Overview

Since the discovery of HIV, scientists have made major inroads in understanding modes of
transmission, infectivity, and pathogenicity. Knowledge about the characteristics and
behavior of this human retrovirus and its complex mechanisms of immunopathogenesis has
helped to develop targeted therapeutic interventions and vaccine strategies. Sophisticated
techniques have been and are being developed to diagnose infection, to monitor immune
decline, to monitor response to therapy and disease progression, and to accurately detect
and diagnose opportunistic diseases. Therapeutic alternatives, especially the nucleoside
analogue antiretroviral drugs, have been tested, approved, and are providing benefit to many
who are HIV-infected. Much has been learned about the complexities of caring for
HIV-infected persons, how to keep them disease-free longer, and how to manage their symptoms
more effectively. In addition, the development of new knowledge from HIV-related research
also has helped to clarify aspects of the human immune response, behavioral interventions,
public health strategies, and social and ethical approaches that contribute to the
understanding and management of other diseases and health conditions. Healthcare
professionals will continue to play a major and significant role in preventing the spread of
HIV infection and in caring for those who are infected or affected by HIV. As the
demographics of HIV infection evolve, both in the United States and around the world, it is
clear that all healthcare professionals in all practice settings will be involved to some
extent with HIV infection. To be effective and provide compassionate care, adequate and
up-to-date information about transmission, prevention, diagnosis, treatment, and care of
HIV-infected individuals must be obtained by all healthcare professionals. They must feel
comfortable with this knowledge in order to provide care, educate patients and others, and
fulfill their professional obligations without undue fear or anxiety.

Attention

This course is designed to fulfill the Washington requirement for
HIV/AIDS education.

Audience

This course is designed for all nurses, physicians, and allied healthcare professionals in Washington involved in the care of patients with HIV/AIDS.

Accreditations & Approvals

NetCE is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
NetCE is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. NetCE has been approved by NBCC as an Approved Continuing Education Provider, ACEP No. 6361. Programs that do not qualify for NBCC credit are clearly identified. NetCE is solely responsible for all aspects of the programs. NetCE, #1092, is approved as a provider for social work continuing education by the Association of Social Work Boards (ASWB) www.aswb.org through the Approved Continuing Education (ACE) Program. NetCE maintains responsibility for the program. ASWB Approval Period: 03/13/2016 to 03/13/2019. Social workers should contact their regulatory board to determine course approval for continuing education credits. NetCE is accredited by the International Association for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.

Designations of Credit

NetCE designates this enduring material for a maximum of 7 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NetCE designates this continuing education activity for 7 ANCC contact hour(s). NetCE designates this continuing education activity for 2 pharmacotherapeutic/pharmacology contact hour(s). NetCE designates this continuing education activity for 8.4 hours for Alabama nurses. NetCE designates this continuing education activity for 3.5 NBCC clock hour(s).
Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 7 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME.
Social workers participating in this intermediate to advanced course will receive 7 Clinical continuing education clock hours, in accordance with the Association of Social Work Boards. AACN Synergy CERP Category A. NetCE is authorized by IACET to offer 0.7 CEU(s) for this program.

Individual State Behavioral Health Approvals

In addition to states that accept ASWB, NetCE is approved as a provider of continuing education by the following state boards: Alabama State Board of Social Work Examiners, Provider #0515; Florida Board of Clinical Social Work, Marriage and Family Therapy and Mental Health Counseling, CE Broker Provider #50-2405; Illinois Division of Professional Regulation for Social Workers, License #159.001094; Illinois Division of Professional Regulation for Licensed Professional and Clinical Counselors, License #197.000185; Illinois Division of Professional Regulation for Marriage and Family Therapists, License #168.000190; Texas State Board of Social Worker Examiners, Approval #3011; Texas State Board of Examiners of Professional Counselors, Approval #1121; Texas State Board of Examiners of Marriage and Family Therapists, Approval #425.

Special Approvals

This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency. This course is designed to fulfill the Washington requirement for HIV/AIDS education. Participants will receive 7 hours of continuing education for completing this course.

Course Objective

In view of the already existing crisis in healthcare in the United States, the problems associated with providing the necessary care for persons with HIV infection or AIDS are significant. The purpose of this course is to address those problems in the discussion of epidemiology, organism characteristics, pathophysiology, transmission, clinical manifestations, complications, treatment advancements, prevention, ethical and legal aspects of care, and workplace concerns.

Learning Objectives

Upon completion of this course, you should be able to:

Discuss the background and significance of the AIDS epidemic, including geographic patterns of transmission.

Discuss the characteristics of the infecting organism and the various HIV tests available.

Describe the transmission and natural history of HIV infection, including risk behaviors and routes of contagion.

Describe the treatments available in the care of patients with HIV, including antiretroviral medications used in patient care.

Discuss the impact of the virus on women living with HIV infection.

Review the transmission of HIV to the infant and child, and discuss care of these infected children.

Summarize issues unique to older persons with HIV infection.

Faculty

Jane C. Norman, RN, MSN, CNE, PhD, received her undergraduate education at the University of
Tennessee, Knoxville campus. There she completed a double major in
Sociology and English. She completed an Associate of Science in
Nursing at the University of Tennessee, Nashville campus and began
her nursing career at Vanderbilt University Medical Center. Jane
received her Masters in Medical-Surgical Nursing from Vanderbilt
University. In 1978, she took her first faculty position and served
as program director for an associate degree program. In 1982, she
received her PhD in Higher Education Administration from Peabody
College of Vanderbilt University. In 1998, Dr. Norman took a
position at Tennessee State University. There she has achieved
tenure and full professor status. She is a member of Sigma Theta
Tau National Nursing Honors Society. In 2005, she began her current
position as Director of the Masters of Science in Nursing Program.

John M. Leonard, MD, Professor of Medicine Emeritus, Vanderbilt University School of Medicine, completed his post-graduate clinical training at the Yale and Vanderbilt University Medical Centers before joining the Vanderbilt faculty in 1974. He is a clinician-educator and for many years served as director of residency training and student educational programs for the Vanderbilt University Department of Medicine. Over a career span of 40 years, Dr. Leonard conducted an active practice of general internal medicine and an inpatient consulting practice of infectious diseases.

Faculty Disclosure

Contributing faculty, John M. Leonard, MD,
has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

Ronald Runciman, MD

Alice Yick Flanagan, PhD, MSW

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist
healthcare professionals to raise their levels of expertise while fulfilling their
continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the
information and recommendations are accurate and compatible with the standards
generally accepted at the time of publication. The publisher disclaims any
liability, loss or damage incurred as a consequence, directly or indirectly, of
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the potential risk of using limited knowledge when integrating new techniques into
practice.

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It is the policy of NetCE not to accept commercial support. Furthermore, commercial
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learners.

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#94731: HIV/AIDS: Epidemic Update for Washington

Review your Transcript to view and print your Certificate of Completion.
Your date of completion will be the date (Pacific Time) the course was electronically
submitted for credit, with no exceptions. Partial credit is not available.

INTRODUCTION

The amount that has been learned and written about human immunodeficiency virus (HIV) infection and disease and its influence on individuals and society is staggering. Since the first recognized case of HIV in the United States more than 30 years ago, researchers have made major inroads in understanding modes of transmission, infectivity, and pathogenicity. Knowledge about the characteristics and behavior of this human retrovirus and its complex mechanisms of immunopathogenesis has helped to develop targeted therapeutic interventions and vaccine strategies. Sophisticated techniques have been and are being developed to diagnose infection, monitor immune decline, monitor response to therapy and disease progression, and accurately detect and diagnose opportunistic diseases.

The immune deficiency characterizing HIV disease is manifested by markedly depressed T
lymphocyte functioning, with a reduction of helper T cells (T4), impaired killer T cell
activities, and increased suppressor T cells (T8). By selectively invading and infecting T
cells, the virus damages the very cell whose function it is to orchestrate the identification
and destruction of the virus as antigen. Other cells with the same molecular makeup might also
become infected. Eventually, the individual's supply of functional T cells becomes depleted.
In a person with a competent immune system, the number of T4 cells ranges from 600–1,200 per
mm3, whereas the patient with HIV might have 0–500 per
mm3 T4 cells [20].

Clinical manifestations of HIV are generally related to opportunistic infections preying on an impaired immune system. These diseases include Pneumocystis carinii pneumonia (PCP) and tuberculosis. The HIV patient commonly succumbs to uncontrollable infection, becoming increasingly debilitated, feverishly ill, malnourished, and often in pain. Lymphadenopathy, pulmonary infiltrates, wasting syndrome, and neurologic abnormalities, such as dementia, tremors, and encephalitis, contribute to the debilitated state. Because HIV travels from cell to cell rather than through the bloodstream, it is usually not susceptible to circulating antibodies of the body's remaining immune system B cells. To date, there is no predictable course of curative treatment [20].

Therapeutic alternatives, especially the nucleoside analogue antiretroviral drugs, have been tested, approved, and are providing benefit to many who are HIV-infected. Much has been learned about the complexities of caring for HIV-infected persons, how to keep them disease-free longer, and how to manage their symptoms more effectively. In addition, the development of new knowledge from HIV-related research has also helped to clarify aspects of the human immune response, behavioral interventions, public health strategies, and social and ethical approaches that contribute to the understanding and management of other diseases and health conditions.

EPIDEMIOLOGY

The epidemiology of HIV infections is presented as it appears
in Africa, Asia, Europe, and the United States. Analysis reveals that the HIV pandemic
continues to escalate throughout developing countries compared to a notable stabilization in
new cases and fatalities in some developed countries. The established healthcare community
became aware of the illness that has since become known as acquired immune deficiency syndrome
(AIDS) in 1981. The tasks of slowing the HIV pandemic and decreasing the mortality rate are
being accomplished by efforts such as diligent treatment of sexually transmitted infections
(STIs), increased condom distribution, and utilization of needle exchange programs. In order
to further decrease HIV transmission, there are increased efforts to strengthen public health
infrastructures, support HIV/STI prevention programs, introduce microbicide, use inexpensive
antiretroviral drug therapy for treatment and prevention of transmission, and improve
educational campaigns [1,44].

Two human immunodeficiency viruses, HIV-1 and HIV-2, have
been identified and both cause AIDS. Researchers in America and England have traced the
ancestry of the HIV-1 virus to two strains found in African red-capped mangabeys and greater
spot-nosed monkeys. The strains most likely combined in chimpanzees that ate both types of
monkeys, resulting in the chimpanzees developing simian immunodeficiency virus (SIV).
Chimpanzees then transmitted the virus to humans, as early as 1930. Genetic studies suggest
that the lower monkeys first became infected with SIV at least 100,000 years ago [2]. HIV-2 is believed to be endemic in West
Africa. Several well-documented cases of HIV-2 infection have been reported in Europeans and
among West Africans residing abroad. Between 1996 and 2009, there were a total of 242 reported
cases of HIV-2 in the United States, the majority of which were associated with immigration
from, travel to, or a sexual partner from West Africa [3]. Differences in the global spread are attributed to differences in
transmissibility and duration of infectiousness [4].

Many countries owe acquisition of HIV infection in their population to sexual transmission or contact with American blood products that were exported before the 1985 HIV screening procedures.

TRANSMISSION PATTERNS

In 1988, the World Health Organization (WHO) established three broad, but distinct, geographic patterns of AIDS transmission, based on worldwide epidemiological studies [5]. It is important to note that, due to a number of factors, these transmission patterns are evolving.

Pattern I

According to these definitions, in pattern I, typical of
industrialized countries with large numbers of reported cases, most cases occurred among
men who have sex with men (MSM) and among urban injection drug users (IDUs). A smaller
percentage of cases are attributed to heterosexual transmission, but this percentage is
increasing significantly. Transmission from exposure to HIV-contaminated blood or blood
products occurred between the late 1970s and 1985, but this has since been largely
controlled through routine blood screening procedures [4].

Pattern II

Pattern II, which was mainly found in areas of central,
eastern, and southern Africa and in some Caribbean countries, is comprised of cases
occurring mostly among heterosexuals. MSM and IDU transmission either does not occur or
occurs at a very low rate. Transmission through contaminated blood and blood products
remains a significant problem [4].

Pattern III

Pattern III is observed in areas of eastern Europe, the
Middle East, Asia, and most of the Pacific basin. HIV appeared to have been introduced to
these areas since the mid-1980s. When the WHO originally described this pattern, only
small numbers of cases had been reported. Generally, cases had occurred among those who
have traveled to endemic areas or who had sexual contact with individuals from endemic
areas. A small number of cases had been reported due to receipt of imported
HIV-contaminated blood [4]. However, the
percentage of HIV-infected population in Asia, particularly in the south and east areas,
is increasing. Although transmission patterns vary geographically, the highest risk groups
appear to be MSM, IDUs, and female sex workers and their clients [6]. Several areas within this pattern group,
such as Russia, China, and India, have been identified as "second wave countries" and are
considered at risk for a future pandemic [7].

WORLDWIDE STATISTICS

According to the Joint United Nations Programme on HIV/AIDS
(UNAIDS), an estimated 35.3 million individuals worldwide were living with HIV/AIDS in 2012,
approximately half of whom were women [8].
Eastern Europe (particularly the Russian Federation), Central Asia, the Middle East, and
Northern Africa have the fastest growing epidemic [8]. It is important to note that despite increases in certain geographic
areas and demographic groups, overall, the rate of new infections is declining. This is due,
in part, to lower prices for anti-AIDS drugs and implementation of prevention programs [8]. Africa is still the hardest hit area, with
71% of all HIV-infected persons living in sub-Saharan Africa in 2012 [8]. In 2003, the U.S. government approved the
purchase of generic drugs to fight the disease in Africa. In that same year, the President's
Emergency Plan for AIDS Relief (PEPFAR) was introduced and implemented [11]. PEPFAR was reauthorized in 2008 and 2013,
with more than $50 billion in funds to HIV/AIDS and to address additional health issues,
including malaria, tuberculosis, maternal health, and clean water [12].

UNITED STATES STATISTICS

As of 2012, an estimated 1.3 million individuals were living with HIV/AIDS in North America [8]. The CDC estimates that approximately 20% of these individuals are unaware of their infection [13]. To compound the problem, only 51% of individuals aware of their infection receive ongoing care. Approximately 72% of all individuals infected with HIV remain untested, without treatment, or both [13]. Unfortunately, this poses a risk both for those who are infected and for others.

Many changes in the progression of the HIV/AIDS epidemic should be considered. Since the first reported cases of HIV in 1981 in the United States, the epidemic continues to vary a great deal between regions, states, and even communities. Populations that are affected by HIV are also shifting. In addition to individuals traditionally considered to be high-risk (e.g., MSM or IDUs), new groups have been identified as being at greater risk. For example, in the beginning stages of the HIV/AIDS epidemic in the United States, white people were chiefly impacted. However, the epidemic now greatly affects racial and ethnic minorities, particularly black Americans, who represent nearly half of all new diagnoses in the United States [15]. Women also have a higher risk of infection. More than half of HIV infections that result from heterosexual contact occur in women.

One should keep in mind when reviewing HIV/AIDS trends that the widespread use of antiretroviral therapy (ART) has resulted in fewer deaths and longer survival [13]. As of 2013, the Centers for Disease Control and Prevention (CDC) report several trends in the HIV/AIDS epidemic [15]:

By region, 40% of persons living with AIDS reside in the South, 30% in the
Northeast, 20% in the West, and 10% in the Midwest.

By race/ethnicity, 42% are black, 37.9% white, 17.4% Hispanic, 1.5% are multiple
race, and less than 1% are American Indian/Alaska Native or Asian/Pacific
Islander.

By gender, 80% of adults and adolescents living with AIDS are male.

The CDC has published guidelines for medical professionals to integrate HIV prevention into the regular medical care of those living with HIV. The three major components of the recommendation are [16]:

Facilitating notification and counseling for sex and needle-sharing partners of infected persons

The CDC, in partnership with other U.S. Department of Health and Human Services agencies and other government and non-government agencies, also launched the initiative Advancing HIV Prevention: New Strategies for a Changing Epidemic [17]. This initiative was a response to increases in HIV infections.

The CDC has also developed a method to better measure the rate of HIV infections in the
United States. The Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS) has
allowed the CDC to more accurately monitor the number of new HIV infections in the United
States, which in turn should facilitate targeted prevention in those populations most in
need [18,19]. STARHS consists of two tests to determine both seropositivity and how
recently the infection was contracted.

WASHINGTON STATE STATISTICS

As of 2013, an estimated 11,500 to 12,700 Washington residents are living with HIV, with the vast majority of cases occurring in King County (7,200 to 8,000) and Pierce County (1,100 to 2,000) [94]. Each year, there are approximately 500 to 600 new cases within the state. The demographics of HIV/AIDS infection in Washington reflect its unique population. The majority of persons living with HIV/AIDS in Washington are white (66%) and male (86%); however, the rate of white males contracting the disease has been decreasing over the past few decades [94]. In 2012, 48% of new cases were among people of color, compared to 32% in 1998. The rates of infection among black persons who are U.S.-born (33 per 100,000/year) and foreign-born (92 per 100,000/year) are approximately 2.3 and 6.4 times that of whites, respectively, although the absolute number of cases is far fewer [94]. Infection rates have also increased significantly among Hispanic men and Asians/Pacific Islanders. While the overall number of persons living with HIV/AIDS in Washington decreased significantly in the 1990s, it has been relatively constant since 2000.

NATURAL HISTORY AND CLASSIFICATION OF HIV INFECTION

VIRAL INVASION

HIV is a retrovirus, carrying genetic information in ribonucleic acid (RNA) rather than in deoxyribonucleic acid (DNA). It infects the T lymphocyte by binding to it at the CD4 receptor site and inserting its RNA into the cell. Through an enzyme called reverse transcriptase, the HIV RNA is converted to DNA. When the T cell is activated to reproduce, its genetic information is now programmed to produce more HIV, at the expense of normal T cell function.

LATENCY PERIOD

Clinical latency, sometimes referred to as the "window" period, is the asymptomatic period of time before the body recognizes the virus and programs antibodies. The exact time that antibodies develop varies, but it is longer in HIV than in many other infectious organisms. The clinical latency period for blood-transmitted HIV infection is thought to be 4 to 7 weeks, and antibody formation after infection through sexual contact is thought to occur 6 to 14 months after the introduction of the virus. The prolonged latency period effectively reduces the accuracy and immediacy of host identification. One of the theories concerning this prolonged latency period is that HIV invades T cells and, in effect, sequesters itself from view of the body's surveillance system, meanwhile multiplying anomalous T cells that are ineffective for purposes of immunity [20].

ACUTE HIV INFECTION

HIV is a protracted infection that passes through several
stages and, if untreated, carries an 80% mortality rate at 10 years. The initial event,
reported in 50% to 90% of patients, is an acute retroviral syndrome characterized as an
infectious, mononucleosis-like illness. Symptoms include fever, sore throat, malaise, rash,
diarrhea, lymphadenopathy, mucocutaneous ulcerations, and weight loss averaging 10 pounds. A
variety of neurologic syndromes, including encephalitis, may occur.

The illness begins 1 to 3 weeks after viral transmission and is self-limited, with an average duration of 2 to 3 weeks. Laboratory abnormalities include lymphopenia, atypical lymphocytosis, and a decreased CD4 cell count. During this early phase, HIV antibody tests are negative, and the diagnosis rests on the demonstration of HIV P24 antigen or, preferably, quantitative plasma HIV RNA. Concentrations of HIV RNA in the blood (viral load) are high during the acute syndrome.

Following the host immune response there is seroconversion with positive serology, and the
viral load decreases considerably, reaching a relatively stable level at about 6 months. At
this juncture, the degree of viral load will dictate the subsequent course. Patients having
high viral concentrations, 105 copies/mL or higher, will have a
relatively rapid course. The prolonged and progressive infection of target lymphocytes
results in an annual average decrease in CD4 count of about
50/mm3.

ASYMPTOMATIC HIV INFECTION

Early-stage HIV infection is characterized by an almost complete absence of symptoms and relatively normal laboratory studies. However, there is a gradual decline in CD4 count with positive serologic and virologic studies indicating past infection and persistent viral activity. Patients may be subclassified based on a laboratory evaluation that includes a complete blood count with differential white blood cell count and a platelet count. Immunologic tests, such as the T-lymphocyte helper and suppressor cell counts, are also an important part of the overall evaluation. Patients with test results that are within normal limits and those who have not yet had complete evaluations should be differentiated from patients whose test results are consistent with HIV-associated defects, lymphopenia, thrombocytopenia, and a decreased number of T4 lymphocytes [4]. The duration of this asymptomatic stage is variable depending on the level of viremia as measured by HIV RNA and is affected by ART.

PERSISTENT GENERALIZED LYMPHADENOPATHY (PGL)

Patients may have persistent generalized lymphadenopathy (PGL) without pain or further disease findings. PGL is defined as palpable lymph node enlargement of 1 cm or greater, at two or more extra-inguinal sites that persists for more than 3 months in the absence of a concurrent illness or condition other than HIV infection to explain the findings. In some cases, lymphadenopathy regresses as HIV disease advances, probably because the architecture of the lymph node is gradually destroyed [4].

DISEASE PROGRESSION AND CLASSIFICATION

Symptomatic infection can be expected to supervene after the CD4 count has decreased to
less than 200/mm3 as this represents the stage of severe
immunodeficiency. The CDC defines late stage HIV infection as AIDS on the basis of two
criteria: characteristic AIDS-defining illness such as PCP, central nervous system (CNS)
toxoplasmosis, or other opportunistic infections or tumors (Kaposi's sarcoma). A variety of
clinical syndromes may supervene at this juncture including dementia, peripheral neuropathy,
wasting syndrome, and chronic diarrhea. In the United States, the most common AIDS-defining
opportunistic diseases are [38]:

PCP

Kaposi's sarcoma

Candidiasis

Cryptococcosis

Cryptosporidiosis

Cytomegalovirus (CMV)

Atypical mycobacteriosis

Systemic herpes

Toxoplasmosis

Tuberculosis

The initial evaluation of the patient with HIV should include assessment of the oral cavity. Several oral manifestations may occur with HIV infection, with increasing incidence associated with decreasing CD4 counts. The majority of patients with AIDS will experience at least one oral complication during the course of the disease, the most common of which are candidiasis, oral hairy leukoplakia (caused by reactivation of the Epstein-Barr virus), HIV-associated periodontal disease (including necrotizing gingivitis or periodontitis), and Kaposi's sarcoma. Salivary gland disease can also occur in HIV/AIDS patients and can cause unilateral or bilateral enlargement of the salivary glands, most commonly the parotid glands. Xerostomia can result from this glandular involvement and may be exacerbated by the use of antiviral medications [61]. These oral manifestations are difficult to treat, and some will be refractory to any approaches. Accurate diagnosis, early and aggressive treatment, and close monitoring are necessary.

In the absence of ART, the average survival is approximately 3.5 years after the patient's
CD4 count has reached 200/mm3 and 1.5 years for the patient who
has developed an AIDS-defining disease. The natural history has been dramatically altered by
ART, especially since the introduction of protease inhibitors and non-nucleoside reverse
transcriptase inhibitors in 1996.

For individuals who acquired AIDS through injection drug use, co-infection with hepatitis C virus is present in 80% of cases. Approximately 25% of all HIV-infected persons in the United States are also infected with hepatitis C virus; 10% are co-infected with hepatitis B virus [39]. Hepatitis C virus is one of the most common causes of chronic liver disease in the United States, and for those individuals co-infected with hepatitis C virus and HIV, liver damage progresses more rapidly. The CDC, the Infectious Diseases Society of America (IDSA), and the National Institutes of Health guidelines recommend that all HIV-infected persons be screened for hepatitis C virus infection [53].

Intervention and treatment of opportunistic diseases and infections is dependent on the ability of the health provider to diagnose, monitor, and educate patients at risk. The main challenge to health providers is choosing those interventions that will alleviate suffering and morbidity, while not exceeding the financial and technical capabilities of the health system [38].

HIV TESTING

Several tests are available to screen for HIV. There are various ways by which these tests function: detection of the antibody, identification of antigens, detection/monitoring of viral nucleic acids, or rendering an estimate of T-lymphocytes (cell phenotyping). Tests used to detect antibodies are the most common and effective way of identifying HIV infection and can be further broken down into two categories [21]:

Supplemental/Confirmatory Tests: Intended to determine all individuals who have positive screening tests, but are not infected (i.e., negates a false-positive), produces few false-positive results

Both types of tests are highly sensitive. Together, they can accurately assess the existence of HIV in blood supply and supplement clinical diagnosis.

The enzyme-linked immunosorbent assay (ELISA), a test originally developed to screen the nation's blood supply, is also common and effective for detecting the presence of HIV antibodies. ELISA is quick, easy to perform, and extremely sensitive; however, its high sensitivity causes a higher rate of false-positive results. There can also be false-negative results with ELISA if the test is conducted before the individual develops antibodies or if the individual is too ill to produce antibodies. When the ELISA test is positive, it should be repeated. If positive again, a supplemental/confirmatory test, such as the Western Blot test, is then used to confirm the presence of HIV antibodies. The Western Blot test uses the more expensive process of electrophoresis; therefore, it is typically used only as a confirmatory test [23].

The OraQuick HIV rapid test detects the presence of antibodies to HIV-1 and produces results within 20 minutes from a single drop of blood. Positive results require confirmation by Western Blot or immunofluorescence assays [17]. Several other rapid HIV antibody screening tests have been approved (Table 1) [22,81]. The benefits of these tests are that they produce results quickly and are cost-effective.

Screening for the antibody is helpful only to the extent that individuals who have been exposed to HIV can be identified. However, not all of these individuals actually carry the virus, nor will all of them show signs of illness. Therefore, several situations are possible:

Exposure: An individual may be exposed to the virus but neither carry it nor contract the disease.

Carrier: The individual may carry the virus with the capability of infecting others without accompanying signs and symptoms.

Terminal Disease: The individual may be infectious,
symptomatic, and terminal. HIV disease becomes AIDS when the immune system is so damaged
that the number of CD4+ T-lymphocyte cells is less than 200 per
mm3 or an opportunistic infection occurs.

It is thought that carriers of the virus who test positive for the antibody can remain as carriers for years with the virus in a dormant state. Although approximately one-third of those who now test positive for the disease eventually will begin to show clinical manifestations, it is thought by some investigators that the percentage of those who go on to develop the disease will eventually approach 100% [20].

As discussed, in addition to these conventional tests there is also a method for determining length of infection [18]. According to the CDC, the BED HIV-1 Capture EIA Assay is based on the observation that the ratio of anti-HIV IgG to total IgG increases with time after HIV infection [24]. If a confirmed HIV-1 positive specimen is reactive on the standard sensitive EIA and has a normalized optical density of <0.8 on the BED assay, the patient is considered recently infected. This test is used in the United States for surveillance purposes.

CONSENT TO TEST

Informed consent should be obtained from each person being tested. Each individual should be fully aware of the limitations of the HIV-antibody test regarding HIV infection and the development of AIDS. The test and its meaning, the reason for ordering the test, and its potential adverse consequences should be understood. The consent also includes information about how the test information will be used. In the state of Washington, no person may undergo HIV testing without the person's consent except in cases of incompetence, double-blinded seroprevalence studies, and/or when the department of labor and industries determines that it is relevant [98].

There have been court cases that have centered on testing without consent; therefore, it is imperative that all healthcare providers follow the procedures concerning consent to test. HIV testing may only be done with patient's consent. Informed consent includes: documentation of consent on the chart, pre- and post-test counseling and referrals. The physician ordering the test is required to tell the patient if the result is positive; offer counseling and appropriate referrals.

Cultural Considerations in Informed Consent

An individual's ability and prerogative to make decisions about treatment
is now seen as a vital expression of autonomy and is a prerequisite to participation in
treatment or interventions. Autonomy, individualism, and self-determination are belief
systems that are highly valued in Western societies, especially in the United States.
Autonomy may be categorized into two groups: first-order autonomy and second-order
autonomy [88]. First-order autonomy is
what Westerners espouse and value: self-determination and autonomy in decision making.
Second-order autonomy, however, is prevalent in collectivistic societies where decision
making is group-oriented and takes into account another decision-maker who is accorded
authority and respect [88]. For example,
in many Asian cultures, particularly if the family system is based on a patriarchal
authority system, a male elder or leader who is regarded as the primary decision-maker is
key in this process of informed consent.

The process of informed consent entails the explicit communication of
information in order for the individual to make a decision. Again, Western cultures value
explicit information, which is centered on American consumerism; believing in having
choices and being able to exercise choices in purchases extends to healthcare. However,
some cultures believe that language and information also shape reality [87]. In other words, explicit information,
particularly if it is bad information, will affect the course of reality.

A signature is required on most Western informed consent forms to
represent understanding and agreement on the part of the individual involved. Yet, this
might be viewed as violation of social etiquette in some cultures. In some cultures (for
example, Egypt), signatures are usually associated with major life events and legal
matters. Therefore, requiring a signature outside these circumstances would imply a lack
of trust, particularly when verbal consent has been given [74].

Furthermore, consent forms often contain technical and legal jargon that
may be overwhelming to the native English speaking individual, but can be much more
daunting for immigrants who may not be English proficient or familiar with various legal
concepts. For some immigrants who have experienced political persecution in their
homelands, asking for a signature on a consent form that contains foreign legal and
technical terms can potentially place them at risk for secondary traumatization, as some
were persecuted, tortured, and forced to sign documents in their homelands [52].

This cultural dissonance can be a challenge to many general healthcare and
mental health practitioners. Cultural experts are highly recommended for consultations to
assist in the interpretation and navigation of the complex web of cultural
interactions.

CONFIDENTIALITY AND ANONYMOUS TESTING

It is important the healthcare professionals protect patients' rights to privacy and confidentiality and offer anonymous testing when appropriate. In Washington, local health officers are required to [97]:

Ensure anonymous HIV testing is reasonably available

Make HIV testing, AIDS counseling, and pretest and post-test counseling available for voluntary, mandatory, and anonymous testing and counseling

Make information on anonymous HIV testing, AIDS counseling, and pretest and post-test counseling available

For purposes of contacting the HIV-positive individual to provide test results
and post-test counseling

To contact persons who have experienced substantial exposure, including sex and
injection equipment-sharing partners, and spouses

To link with other name-based public health disease registries when doing so
will improve ability to provide needed care services and counseling and disease
prevention

Destroy documentation of referral information containing identities and identifying information on HIV-infected individuals and at-risk partners of those individuals immediately after notifying partners or within three months, whichever occurs first

According to the Washington Department of Health, sharing the results of any sexually transmitted infection (STI) testing is restricted [96]. The exchange of medical information among healthcare providers and within facilities in order to provide healthcare services to the patient is permitted, and the results of HIV testing may be released to the following recipients:

The subject of the test

A person with a release of information from the tested person

Health officials in accordance with reporting requirements for diagnosed STIs

Facilities that collect blood, tissue, or semen

Health officials, first responders, or victims of sexual assault who petition the court to order testing

A person allowed access to information by a court order

Local law enforcement if health officers have exhausted procedures to stop behaviors that present a danger to the health of the public

Exposed persons who are notified because releasing the identity of the infected person is necessary

Payers of health claims

Agencies or guardians responsible for children younger than 14 years of age with an STI

However, HIV testing results should be released to approved parties with the following warning: "This information has been disclosed to you from records whose confidentiality is protected by state law. State law prohibits you from making any further disclosure of it without the specific written consent of the person to whom it pertains, or as otherwise permitted by state law. A general authorization for the release of medical or other information is NOT sufficient for this purpose" [96].

TRANSMISSION OF HIV

Transmission of HIV results from intimate contact with blood and body secretions, excluding saliva and tears. The most common modes of transmission are sexual contact, administration of contaminated blood and blood products, contaminated needles, and mother-to-fetus. Blood transfusions of whole blood, packed cells, and fresh frozen plasma are most unlikely to be the cause of transmission with the more sophisticated crossmatching and antibody screening measures; individuals needing specific blood components (such as factor VIII and frequent plasma replacement) are more at risk [20].

On the basis of newly reported cases, the transmission
categories are [15]:

Male-to-male sexual contact

IDUs

MSM who inject drugs

High-risk heterosexual contact

Blood transfusion

Hemophilia/coagulation disorder

Perinatal transmission

No reported risk category

SEXUAL TRANSMISSION OF HIV

HIV has been isolated from blood, seminal fluid,
pre-ejaculate, vaginal secretions, urine, cerebrospinal fluid, saliva, tears, and breast
milk of infected individuals. Whether HIV infects spermatozoa is controversial. Reports of
the removal of infected cells from semen, allowing artificial insemination without
seroconversion, support the idea that spermatozoa are not infected. No cases of HIV
infection have been traced to saliva or tears [32].

The virus is found in greater concentration in semen than in vaginal fluids, leading to a hypothesis that male-to-female transmission could occur more easily than female-to-male. Sexual behavior that involves exposure to blood is likely to increase transmission risks. Transmission could occur through contact with infected bowel epithelial cells in anal intercourse in addition to access to the bloodstream through breaks in the rectal mucosa.

Although all HIV-seropositive people are potentially infectious, there is widespread variation in the seropositivity and seroconversion of their sexual partners. Factors that could explain this variability include differences in sexual practices and numbers of sexual contacts, susceptibility of the partner, differences in viral strains, changing degrees of infectiousness of the HIV-infected person over time, co-factors that enhance or limit transmission, genetic resistance, or a combination of these factors.

Posing the highest risk of infection is unprotected anal
receptive intercourse, followed by unprotected vaginal intercourse. Risk is reduced through
the use of latex condoms. For the wearer, latex condoms provide a mechanical barrier
limiting penile exposure to infectious cervical, vaginal, vulvar, or rectal secretions or
lesions. Likewise, the partner is protected from infectious pre-ejaculate, semen, and penile
lesions. Oil-based lubricants may make latex condoms ineffective and should not be used.
Water-soluble lubricants are considered safe. Natural membrane condoms (made from lamb
cecum) contain small pores and do not block HIV passage.

It is estimated that latex condom efficacy in the prevention of HIV transmission is approximately 85% [90]. Although abstinence from sexual contact is the sole way to absolutely prevent transmission, using a latex condom to prevent transmission of HIV is more than 10,000 times safer than engaging in unprotected sex [89]. Sexual activity in a mutually monogamous relationship in which neither partner is HIV-infected and no other risk factors are present is considered safe [4].

The phenomenon of men who identify publicly as heterosexual and generally have committed relationships with women, but who also engage in sexual activity with other men, termed being on the "down low" (DL), may be a transmission bridge to heterosexual women. In a 2005 study, researchers surveyed 328 MSM in 12 cities and found that 43% of black men, 26% of Hispanic men, and 7% of white men reported being on the down low [25]. It is important to note that men on the down low are not the only MSM who report having sexual contact with women. In a larger study of 5,000 HIV-positive MSM, 22% of gay-identified black MSM and 61% of bisexual-identified black MSM reported having had sex with a woman in the past five years [49].

However, a 2009 study of 1,151 black MSM in New York City and Philadelphia challenged the association of down low identity with increased HIV risk behavior [9]. Of the respondents, 31% identified as down low, and of those, 11% identified as heterosexual, 25% identified as homosexual, and the remainder presumably identified as bisexual. Down low MSM were found to engage in fewer instances of unprotected receptive anal sex compared to non-down low MSM and were also less likely to be HIV positive. The authors concluded that predicting risk based on actual sexual behaviors is much more accurate than trying to associate a particular identity with HIV risk for female sex partners of MSM, as male sexual identity does not predict the frequency of sexual contact with women.

Oral Sex

Numerous studies have demonstrated that oral sex can result in the transmission of HIV and other STIs. While the risk of HIV transmission through oral sex is much smaller than the risk from anal or vaginal sex, there are several co-factors that can increase this risk, including oral ulcers, bleeding gums, genital sores, and the presence of other STIs. Prevention includes the use of latex condoms, a natural rubber latex sheet, plastic food wrap, a condom cut into a sheet, or a dental dam, all of which serve as a physical barrier to transmission [26].

BLOOD DONOR PRODUCTS

It has been estimated that an HIV-infected drop of human
blood contains 1 to 100 live virus particles. In comparison, a drop infected with hepatitis
B virus has 100 million to 1 billion organisms. Even so, HIV is transmitted via blood,
primarily through sharing of contaminated needles among IDUs and, rarely, through blood
transfusion. Transmission of HIV-1 has occurred after transfusion of the following
components: whole blood, packed red blood cells (including washed and buffy coat poor),
fresh frozen plasma, cryoprecipitate, platelets, and plasma-derived products, depending on
the production process.

With the implementation of a donor screening program of the
nation's blood supply in 1985 and advances in the treatment of donated blood products, blood
transfusion is now even safer; the current risk of transmission of AIDS through this route
is estimated to be 1 in 225,000. A somewhat higher estimate of 1 in 40,000 to 1 in 60,000 is
reported from areas that have a high prevalence of HIV-1 infection. It is possible that
before blood screening implementation, more than 12,000 people were infected. A large
percentage of hemophiliacs acquired HIV in this manner. Donor screening, HIV testing, and
heat treatment of the clotting factor have greatly reduced the risks. To further decrease
the possibility of HIV transmission through transfusion of blood and blood products,
patients scheduled to undergo elective surgery are increasingly advised to make predeposited
blood donations for intraoperative autotransfusion.

To date, screening tests cannot detect either recently HIV-1-infected people who have not yet developed antibody (the "window period") or HIV antibody-negative patients who have AIDS. Donating procedures include an interview for risk factors and the ability of the potential donor to exclude their blood from being used. Very few transfusion-related cases of HIV infection have been reported in the United States since 1992, when all U.S. blood centers began to test donations for antibodies to both HIV-1 and HIV-2 [10]. Clinicians should recommend HIV antibody testing for all people transfused between January 1978 and March 1985, although the likelihood of new cases from this transmission category is low [4].

NEEDLE SHARING

Transmission of HIV among injecting drug users occurs primarily through contamination of injection paraphernalia with infected blood. The risk of sustaining HIV infection from a needle stick with infected blood is approximately 1 in 300. Behavior such as needle sharing, "booting" the injection with blood, and performing frequent injections increases the risk. Cocaine use (by injection or smoking) is associated with a higher prevalence of HIV infection. This may in part be attributed to the exchange of cocaine for sex. Sharing of equipment is common due to legal and financial restrictions and cultural norms. Geographically, the rate of infection varies; 80% of New York City addict needle sharers are infected, as opposed to lower rates in other metropolitan area clusters. Secondary transmission occurs to children and sexual partners. Preventative strategies include drug treatment, onsite medical care in a drug treatment program, recruitment of "street" outreach workers for intensive drug and sex "risk reduction" educational campaigns, teaching addicts to sterilize their equipment between use, the free provision or exchange of sterile injection equipment (as allowed by law), distribution of condoms and bleach to clean drug use equipment, or a combination of these interventions [4].

Health professionals should stress the following messages when they counsel IDUs [85]:

The best way for you to prevent HIV and hepatitis B and C virus transmission is to NOT inject drugs.

Entering substance abuse treatment can help you reduce or stop injecting. This will lower your chances of infection.

Get vaccinated against hepatitis A and hepatitis B. You can prevent these kinds of viral hepatitis if you get vaccinated.

If you cannot or will not stop injecting, you should:

Use a new, sterile syringe obtained from a reliable source to prepare and divide
drugs for each injection.

Never reuse or share syringes, water, cookers, or cottons.

Use sterile water to prepare drugs each time, or at least clean water from a
reliable source.

Keep everything as clean as possible when injecting.

If you cannot use a new, sterile syringe and clean equipment each time, then disinfecting with bleach may be better than doing nothing at all:

Fill the syringe with clean water and shake or tap. Squirt out the water and throw it away. Repeat until you do not see any blood in the syringe.

Completely fill the syringe with fresh, full-strength household bleach. Keep it in the syringe for 30 seconds or more. Squirt it out and throw the bleach away.

Fill the syringe with clean water and shake or tap. Squirt out the water and throw it away.

If you do not have any bleach, use clean water to vigorously flush out the syringe. Fill the syringe with water and shake or tap it. Squirt out the water and throw it away. Repeat several times.

It is important to note that a disinfected syringe is not a sterile syringe. The best option is always to use a new, sterile syringe with every injection.

PERINATAL TRANSMISSION

In the absence of prophylactic treatment, approximately 30% to 50% of children born to HIV-infected mothers will contract HIV infection. HIV is transmitted to infants by transplacental spread from mother to fetus in utero, during parturition, or through breastfeeding after birth. Because infants have underdeveloped natural resistance systems, they are highly susceptible to many infections, including HIV. Both uninfected and infected infants have been born to mothers who have previously borne an infected infant. Studies have dramatically shown the beneficial effect of treating pregnant women and newborns with Zidovudine (ZDV) to prevent transmission to the child, resulting in declines in the incidence of perinatally acquired AIDS [75]. Standard screening of all pregnant women is necessary to reduce transmission of HIV to infants.

Worldwide, perinatal transmission accounts for most HIV
infections among children. In the United States in 2010, 143 infants were born with HIV
infection, down from more than 1,700 in the mid-1990s [75]. In all, perinatal transmission has markedly decreased, by more than
80%, since 1991. This dramatic decrease is mainly attributed to the use of ART [28]. Other strategies for reducing perinatally
acquired HIV infection have included preventing HIV infection among women and, for
HIV-infected women, avoiding pregnancy or refraining from breastfeeding. On February 21,
1994, the National Institutes of Health's National Institute of Allergy and Infectious
Diseases (NIAID) and National Institute of Child Health and Human Development (NICHD)
announced preliminary results from a randomized, multicenter, double-blind clinical trial of
ZDV to prevent HIV transmission from mothers to their infants. This report summarizes the
interim results of that trial, which indicate effectiveness of ZDV for prevention of
perinatal transmission. Based on these interim findings, NIAID accepted the recommendation
of an independent data and safety monitoring board to terminate enrollment into the trial
and to offer ZDV to women in the group who had received the placebo but had not yet
delivered and to their infants younger than 6 weeks of age [29].

OCCUPATIONAL EXPOSURES

Transmission due to occupational exposure of healthcare workers has occurred in needlestick accidents and blood splashes to the mucous membranes. Needlestick is the most common route. Thousands of healthcare personnel who were so exposed have been studied, and only 57 cases of well-documented infection have been reported in the United States (24 of which were nurses) [34]. The risk of infection through this route is low, and every effort should be made to decrease the exposure rate. Educational efforts, implementation of engineering controls in needled and sharp-edged medical devices, the use of hard plastic needle disposal units where these devices are most frequently used, and the development of procedural details to avoid blood and body fluid contact have greatly reduced the exposure rate. Healthcare personnel must apply universal precautions, as discussed in the Occupational Safety and Health Administration (OSHA) Bloodborne Pathogens standard regulations, to all activities to avoid contact with human fluids [4].

All body fluids should be considered potentially infectious. Contaminated needles or other sharps should not be bent, recapped or removed, unless specifically required by a particular medical or dental procedure. All healthcare professionals should have access to and use personal protective equipment, such as gloves, gowns, face shields, masks, eye protection, and ventilation devices, to limit exposure to potentially infectious fluids. OSHA standards require that single-use gloves be worn when contact with blood or other potentially infectious substance, including mucous membranes, can be reasonably anticipated [35].

POSTEXPOSURE PROPHYLAXIS (PEP)

This section, Postexposure Prophylaxis, is from the Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis [36].

Definitions of Healthcare Personnel and Exposure

The definitions of HCP and occupational exposures are unchanged from those used in 2001 and 2005. The term HCP refers to all paid and unpaid persons working in healthcare settings who have the potential for exposure to infectious materials including body substances (e.g., blood, tissue, and specific body fluids), contaminated medical supplies and equipment, or contaminated environmental surfaces. HCP might include, but are not limited to, emergency medical service personnel, dental personnel, laboratory personnel, autopsy personnel, nurses, nursing assistants, physicians, technicians, therapists, pharmacists, students and trainees, contractual staff not employed by the healthcare facility, and persons not directly involved in patient care but potentially exposed to blood and body fluids (e.g., clerical, dietary, housekeeping, security, maintenance, and volunteer personnel). The same principles of exposure management could be applied to other workers with potential for occupational exposure to blood and body fluids in other settings.

An exposure that might place HCP at risk for HIV infection is defined as a percutaneous injury (e.g., a needlestick or cut with a sharp object) or contact of mucous membrane or nonintact skin (e.g., exposed skin that is chapped, abraded, or afflicted with dermatitis) with blood, tissue, or other body fluids that are potentially infectious. In addition to blood and visibly bloody body fluids, semen and vaginal secretions also are considered potentially infectious. Although semen and vaginal secretions have been implicated in the sexual transmission of HIV, they have not been implicated in occupational transmission from patients to HCP. The following fluids also are considered potentially infectious: cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, and amniotic fluid. The risk for transmission of HIV infection from these fluids is unknown; the potential risk to HCP from occupational exposures has not been assessed by epidemiologic studies in healthcare settings. Feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious unless they are visibly bloody.

Any direct contact (i.e., contact without barrier protection) to concentrated virus in a research laboratory or production facility requires clinical evaluation. For human bites, clinical evaluation must include the possibility that both the person bitten and the person who inflicted the bite were exposed to bloodborne pathogens. Transmission of HIV infection by this route has been reported rarely, but not after an occupational exposure.

HIV PEP

The recommendations in this section apply to situations in which a healthcare provider has been exposed to a source person who either has, or there is a reasonable suspicion of, HIV infection. These recommendations reflect expert opinion and are based on limited data regarding safety, tolerability, efficacy, and toxicity of PEP. If PEP is offered and taken and the source is later determined to be HIV-negative, PEP should be discontinued and no further HIV follow-up testing is indicated for the exposed provider. Because the great majority of occupational HIV exposures do not result in transmission of HIV, the potential benefits and risks of PEP (including the potential for severe toxicity and drug interactions, such as may occur with oral contraceptives, H2-receptor antagonists, and proton pump inhibitors, among many other agents) must be considered carefully when prescribing PEP. Because of the complexity of selecting HIV PEP regimens, whenever possible, these recommendations should be implemented in consultation with persons who have expertise in the administration of antiretroviral therapy and who are knowledgeable about HIV transmission. Reevaluation of exposed HCP is recommended within 72 hours post-exposure, especially as additional information about the exposure or source person becomes available.

Recommended Protocol for PEP

A regimen containing three (or more) antiretroviral drugs is now recommended routinely for all occupational exposures to HIV (Table 2). Examples of recommended PEP regimens include those consisting of a dual nucleoside reverse transcriptase inhibitor (NRTI) backbone plus an integrase strand transfer inhibitor (INSTI), a protease inhibitor (boosted with ritonavir), or a non-nucleoside reverse transcriptase inhibitor. Other antiretroviral drug combinations may be indicated for specific cases (e.g., an exposure to a source patient harboring drug-resistant HIV), but should only be prescribed after consultation with an expert in the use of antiretroviral agents.

Timing of PEP Initiation

Animal studies have suggested that PEP is most effective when begun as soon as possible after the exposure and that PEP becomes less effective as time from the exposure increases, PEP should be initiated as soon as possible, preferably within hours of exposure. Occupational exposures to HIV should be considered urgent medical concerns and treated immediately. For example, a surgeon who sustains an occupational exposure to HIV while performing a surgical procedure should promptly scrub out of the surgical case, if possible, and seek immediate medical evaluation for the injury and PEP. Additionally, if the HIV status of a source patient for whom the practitioner has a reasonable suspicion of HIV infection is unknown and the practitioner anticipates that hours or days may be required to resolve this issue, antiretroviral medications should be started immediately rather than delayed.

Although animal studies demonstrate that PEP is likely to be less effective when started more than 72 hours postexposure, the interval after which no benefit is gained from PEP for humans is undefined. If initiation of PEP is delayed, the likelihood increases that benefit might not outweigh the risks inherent in taking antiretroviral medications. Initiating therapy after a longer interval (e.g., 1 week) might still be considered for exposures that represent an extremely high risk for transmission. The optimal duration of PEP is unknown; however, duration of treatment has been shown to influence success of PEP in animal models. Because 4 weeks of PEP appeared protective in animal, in vitro, and occupational studies, PEP should be administered for 4 weeks, if tolerated.

PEP for Pregnant HCP

The decision to offer HIV PEP to a pregnant or breastfeeding healthcare provider should be based upon the same considerations that apply to any provider who sustains an occupational exposure to HIV. The risk of HIV transmission poses not only a threat to the mother, but also to the fetus and infant, as the risk of mother-to-child HIV transmission is markedly increased during acute HIV infection during pregnancy and breastfeeding. However, unique considerations are associated with the administration of antiretroviral agents to pregnant HCP, and the decision to use antiretroviral drugs during pregnancy should involve both counseling and discussion between the pregnant woman and her healthcare provider(s) regarding the potential risks and benefits of PEP for both the healthcare provider and for her fetus.

The potential risks associated with antiretroviral drug exposure for pregnant women, fetuses, and infants depend on the duration of exposure as well as the number and type of drugs. Information about the use of newer antiretroviral agents, administered as PEP to HIV-uninfected pregnant women, is limited. For reasons including the complexities associated with appropriate counseling about the risks and benefits of PEP, as well as the selection of antiretroviral drugs in pregnant women, expert consultation should be sought in all cases in which antiretroviral medications are prescribed to pregnant HCP for PEP.

Postexposure Testing and Follow-Up

HCP who have experienced occupational exposure to HIV should receive follow-up counseling, postexposure testing, and medical evaluation regardless of whether they take PEP. Greater emphasis is placed upon the importance of follow-up of HCP on HIV PEP within 72 hours of exposure and improving follow-up care provided to exposed HCP. Careful attention to follow-up evaluation within 72 hours of exposure can: 1) provide another (and perhaps less anxiety-ridden) opportunity to allow the exposed HCP to ask questions and for the counselor to make certain that the exposed HCP has a clear understanding of the risks for infection and the risks and benefits of PEP, 2) ensure that continued treatment with PEP is indicated, 3) increase adherence to HIV PEP regimens, 4) manage associated symptoms and side effects more effectively, 5) provide an early opportunity for ancillary medications or regimen changes, 6) improve detection of serious adverse effects, and 7) improve the likelihood of follow-up serologic testing for a larger proportion of exposed personnel to detect infection. Closer follow- up should in turn reassure HCP who become anxious after these events. The psychological impact of needlesticks or exposure to blood or body fluid should not be underestimated for HCP. Exposed personnel should be advised to use precautions (e.g., use of barrier contraception, avoid blood or tissue donations, pregnancy, and if possible, breastfeeding) to prevent secondary transmission, especially during the first 6 to 12 weeks postexposure. Providing HCP with psychological counseling should be an essential component of the management and care of exposed HCP.

HIV testing should be used to monitor HCP for seroconversion after occupational HIV exposure. After baseline testing at the time of exposure, follow-up testing should be performed at 6 weeks, 12 weeks, and 6 months after exposure. Use of fourth generation HIV Ag/Ab combination immunoassays allow for earlier detection of HIV infection. If a provider is certain that a fourth generation combination HIV Ag/Ab test is used, HIV follow-up testing could be concluded earlier than 6 months after exposure. In this instance, an alternative follow-up testing schedule could be used (e.g., baseline testing, 6 weeks, and then concluded at 4 months after the exposure). Extended HIV follow-up (e.g., for 12 months) is recommended for HCP who become infected with HCV after exposure to a source who is co-infected with HIV and HCV. Whether extended follow-up is indicated in other circumstances (e.g., exposure to a source co-infected with HIV and HCV in the absence of HCV seroconversion or for exposed persons with a medical history suggesting an impaired ability to mount an antibody response to acute infection) is unknown.

NONOCCUPATIONAL POSTEXPOSURE PROPHYLAXIS (NPEP)

In 2016, the CDC published updated guidelines for the
recommendation of PEP for nonoccupational exposures. This section is taken from Updated
Guidelines for Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use,
or Other Nonoccupational Exposure to HIV—United States, 2016 [37].

Healthcare providers should evaluate persons rapidly for nPEP when care is sought within
72 hours after a potential nonoccupational exposure that presents a substantial risk for HIV
acquisition. All persons considered for nPEP should have determination of their HIV
infection status by HIV testing, preferably by using rapid combined Ag/Ab, or antibody blood
tests. If rapid HIV blood test results are unavailable, and nPEP is otherwise indicated, it
should be initiated without delay and can be discontinued if the patient is later determined
to have HIV infection already or the source is determined not to have HIV infection. nPEP is
recommended when the source of the body fluids is known to be HIV-positive and the reported
exposure presents a substantial risk for transmission. nPEP is not recommended when the
reported exposure presents no substantial risk of HIV transmission or when care is sought
more than 72 hours after potential exposure. A case-by-case determination about the nPEP is
recommended when the HIV infection status of the source of the body fluids is unknown and
the reported exposure presents a substantial risk for transmission if the source did have
HIV infection.

All persons evaluated for possible nPEP should be provided any indicated prevention,
treatment, or supportive care for other exposure-associated health risks and conditions
(e.g., bacterial sexually transmitted infections, traumatic injuries, hepatitis B virus and
hepatitis C virus infection, or pregnancy). All persons who report behaviors or situations
that place them at risk for frequently recurring HIV exposures (e.g., injection drug use,
sex without condoms) or who report receipt of a course of nPEP in the past year should be
provided risk-reduction counseling and intervention services, including consideration of
pre-exposure prophylaxis.

ORGAN TRANSPLANTATION

Because these procedures are less common than other transmission-related activities, there have been very few case reports of HIV acquisition by this route. HIV has been transmitted via transplanted kidneys, liver, heart, pancreas, bone, and, possibly, skin grafts and through artificial insemination. HIV testing is used in these circumstances to rule out infection. Most cases of transmission through transplants of organs, bone, or tissue occurred before HIV screening was available. However, in November 2007, four organ transplant recipients contracted HIV and hepatitis C from a single organ donor [79]. This was the first case of HIV infection resulting from transplantation since 1985. The donor was tested via ELISA for HIV and hepatitis, but the test resulted in a false negative. As with blood transfusions, donors testing antibody seronegative may pass HIV infection on to recipients [4]. The use of nucleic acid testing and reconsideration of the use of high-risk donors have both been recommended to ensure the safety of donor recipients [79].

In 2009, a living donor transmitted HIV to a kidney transplant recipient [14]. The donor had been screened 79 days prior to the transplant, but had not been retested. The CDC now recommends screening live donors no more than 7 days before organ recovery.

MANAGEMENT OF HIV INFECTION

Primary physicians in consultation with specialists are playing an increasing role in the care of HIV-infected individuals. It is not possible for all care to be delivered by infectious disease and oncology specialists. Moreover, with early ART and prophylaxis for opportunistic infections, HIV disease shares features of other multisystem, chronic diseases characterized by acute exacerbations and end-stage manifestations.

SCREENING AND COUNSELING

Primary care physicians should provide risk factor assessment of their patients and, when appropriate, screening for HIV infection with pretest and post-test counseling. HIV screening may be completed after notifying the patient that the test will be performed and allowing the patient to opt out of or defer testing. Assent is inferred unless the patient declines testing [41]. Opt-out screening does not require the pre-test counseling and explicit written consent associated with opt-in programs. Patients have reported less anxiety with opt-out screening as compared to opt-in [41].

Pretest counseling, which should be conducted when feasible, should include review of risk factors for HIV infection, discussion of safer sex, and the meaning of a positive test. It is recommended that, while basic information regarding HIV should be provided, extensive counseling may be eliminated if it is perceived to be a barrier to testing [41]. Pretest counseling requirements vary by state. Post-test counseling should include information on steps to lower HIV risk. Post-test counseling for the patient who has a positive test result should include [40,41]:

Addressing emotional response and concerns associated with being HIV positive

Treatment options

A referral for HIV and mental health care

Emphasis on the importance of notifying the patient's sex or drug use partner(s)

Information about how to avoid transmitting HIV to others

The Panel on Antiretroviral Guidelines for Adults and Adolescents
recommends that every HIV-infected patient entering into care should have a complete
medical history, physical examination, and laboratory evaluation, and should be counseled
regarding the implications of HIV infection. The goals of the initial evaluation are to
confirm the diagnosis of HIV infection, to obtain appropriate baseline historical and
laboratory data, to ensure patient understanding about HIV infection and its transmission,
and to initiate care as recommended in HIV primary care guidelines and the guidelines for
prevention and treatment of HIV-associated opportunistic infections.

In newly diagnosed or identified patients, the use of partner services is recommended. Partner services are a broad array of services that should be offered to persons with HIV infection and their partners [30]. A critical function of partner services is partner notification, a process through which infected persons are interviewed to elicit information about their partners, who can then be confidentially notified of their possible exposure or potential risk. Other functions of partner services include prevention counseling, testing for HIV and other types of STIs, hepatitis screening and vaccination, treatment or linkage to medical care, linkage or referral to other prevention services, and linkage or referral to other services. The rationale for use of partner services is that appropriate use of public health resources to identify infected persons, notify their partners of their possible exposure, and provide infected persons and their partners a range of medical, prevention, and psychosocial services can have positive results [30].

APPROACH TO TREATMENT

Patients with HIV infection should be seen at regular intervals by a primary care provider to perform periodic physical examinations, monitor prognostic markers (e.g., CD4 count, viral load), initiate and monitor antiviral and prophylactic therapy, provide supportive counseling, and offer assistance with terminal care. Specialists should be consulted for patients intolerant of standard drugs, those in need of systemic chemotherapy, and those with complicated opportunistic infections. In some cases, a single specialist consultation with follow-up to the primary care physician will provide the needed expertise while ensuring continuity of care.

Standard laboratory tests for patients with HIV infection may include [42]:

HIV serology: Standard HIV serologic testing by the ELISA method and confirmation by the Western Blot test carries a sensitivity and specificity exceeding 99%. Suspect patients with negative or indeterminate results should have repeat serologic testing in 2 to 3 months.

Quantitative HIV RNA: The measurement of HIV RNA in plasma is extremely important for determining prognosis and monitoring response to treatment. Combination antiretroviral regimens will usually produce a 50% decrease in total viral load within just a few days. HIV RNA assays should be performed approximately one month after initiation of new treatment and at 4-month intervals thereafter.

CD4 count: The CD4 count is essential for evaluating the status of the immune system. In healthy adults, levels average approximately 600–1400/mm3. It is recommended that CD4 counts be performed at 4-month intervals for most patients.

Complete blood count (CBC): Anemia, leukopenia, and thrombocytopenia are common in HIV patients in relation to progressive primary viral infection, super-infection with disseminated opportunistic pathogens, and as a complication of ART. The CBC should be repeated at 3- to 4-month intervals or more frequently if the patient's clinical course is unstable or there is prior evidence of bone marrow suppression.

Chest x-ray: Standard chest x-ray should be performed on the initial evaluation of persons found to be HIV-positive with pulmonary symptoms or a positive tuberculosis test. This provides a baseline reference for a patient population at high risk for opportunistic pulmonary complications.

Hepatitis serology and liver chemistry panel: These are indicated in the early evaluation of most patients because of the high incidence of concurrent hepatitis. Appropriate tests include detection of serologic markers for hepatitis B and C.

Syphilis serology: Standard serologic testing for syphilis is recommended annually in patients who are sexually active.

PPD skin test: The PPD tuberculin skin test should be performed annually for patients in high-risk categories including those with HIV infection. Induration greater than or equal to 5 mm is defined as a positive result in patients with HIV infection.

Fasting blood glucose and serum lipids: These tests are helpful if the patient is considered at risk for cardiovascular disease as ART can affect metabolic processes.

Genotypic resistance testing: For all patients who have pretreatment HIV RNA >1,000 copies/mL, genotypic resistance testing should be conducted.

ANTIRETROVIRAL THERAPY (ART)

Strategies for the treatment of HIV infection are based on an understanding of the molecular biology of HIV and the life cycle of the virus within the host cell. Antiviral agents have been developed that act predominately on processes specific to the virus particle in order to preserve the integrity of the host cell. Several potential strategies specifically aimed at interruption of the viral life cycle have been defined, including:

Preventing the virus from attaching to the CD4 receptor of the T4 lymphocyte

Interfering with uncoating of the virus within the cell, the first essential step in proviral integration into cellular DNA

Inhibiting reverse transcriptase (RT), a viral enzyme specific to retroviruses, which enables the virus to make a DNA copy from single-stranded viral RNA prior to integration into cellular DNA

Blocking viral regulatory and transactivating proteins, which are involved in the transcription and translation of viral RNA proteins from proviral DNA as the virus goes from the quiet, integrated state to active replication

Inhibiting protease, a viral enzyme responsible for the cleaving of viral proteins both before proviral integration and as the viral particles recombine into functional proteins needed for viral maturation

Preventing viral assembly and budding out of the cell

Blocking the viruses' ability to enter CD4 cells

ART combines 6 classes of agents: NRTIs, non-nucleoside reverse transcriptase inhibitors
(NNRTIs), protease inhibitors (PIs), fusion inhibitors, integrase inhibitors, and chemokine
(C-C motif) receptor 5 (CCR5) antagonists. Initiated in 1995 in the United States, ART
regimens have been effective in dramatically decreasing HIV-related morbidity and mortality
and should be considered for all HIV-infected persons who qualify for such therapy. In
addition to combination therapy, the sequencing of drugs and the preservation of future
treatment options are also important. Three types of combination regimens may be employed as
initial therapy. These include: NNRTI-based regimens, PI-based regimens, and rarely,
triple-NRTI regimens. The goal of these regimens is to "save" one or more classes of drugs
for later use [42]. The U.S. Department of
Health and Human Services, in their revised guidelines for the use of antiretroviral agents
in HIV-infected adults and individuals, have made the distinction between NNRTI-based
regimens and PI-based regimens. Treatment is also classified as "recommended" or
"alternative." These changes may simplify therapeutic decisions for clinicians [42,43].

Prior to 1996, only one class of antiviral drugs, the NRTIs, was available for treatment
of HIV infection. Nucleoside inhibitors act against only one step in the virus life cycle,
inhibiting RT. The introduction of NNRTIs and PIs, which act at a different site or by a
different mechanism, has revolutionized strategies for the treatment of this infection. For
the first time, combination drug regimens employing two or more classes of antiretrovirals
achieved the goal of no detectable virus, resulting in prolonged survival in many previously
untreated patients. As noted above, there are 6 major classes of antiretroviral
drugs.

Nucleoside Reverse Transcriptase Inhibitors

NRTIs, used singularly or in combination, can increase CD4 count, decrease viral load, and prolong survival. Sequential monotherapy is followed eventually by clinical failure based on the emergence of drug resistance in HIV; therefore, these agents are rarely used alone in initial therapies [42]. Combinations of two NRTIs result in better viral suppression, more sustained CD4 counts and decreased emergence of resistance. Available NRTI agents include: abacavir (Ziagen, ABC); zidovudine (Retrovir, ZDV, AZT); didanosine (Videx, ddl); stavudine (Zerit, d4T); lamivudine (Epivir, 3TC); and emtricitabine (Emtriva, Coviracil, FTC). Tenofovir (Viread, TDF) is often categorized as an NRTI but is actually a nucleotide reverse transcriptase inhibitor.

Non-Nucleoside Reverse Transcriptase Inhibitors

NNRTIs have a high affinity for the active site of HIV-RT. When used as a single agent, this class is associated with emergence of resistance in as little as 6 weeks. Thus, these drugs should not be used as single agents but are best employed in combination regimens for patients who have not received prior ART. Available agents include: efavirenz (Sustiva, EFV); delavirdine (Rescriptor, DLV); nevirapine (Viramune, NVP); rilpivirine (Edurant); and etravirine (Intelence).

Protease Inhibitors (PIs)

Development of a mature infectious virus depends upon
enzymatic cleavage of HIV transcribed polyprotein by HIV protease. In binding to the
active site of the HIV protease, PIs interrupt the formation of mature infectious
particles and reduce viral replication by as much as 99%. Resistance to PIs develops
rapidly when these agents are used alone. However, in combination with nucleoside analogs
the effect can last for years, often resulting in a reduction of viral load to
undetectable levels. Available agents include: indinavir (Crixivan, IDV); nelfinavir
(Viracept, NFV); ritonavir (Norvir, RTV); saquinavir (Invirase, Fortovase, SQV);
lopinavir/ritonavir (Kaletra); atazanavir (Reyataz, ATZ); tipranavir (Aptivus, TPV);
darunavir (Prezista; DRV); and fosamprenavir (Lexiva, FPV).

It was discovered that both fatal and non-fatal intracranial hemorrhage occurred in 13 out of 6,840 individuals using tipranavir in clinical trials. It was also found that tipranavir can inhibit platelet aggregation [45]. The FDA Center for Drug Evaluation and Research has approved safety labeling changes for tipranavir that include warnings of the increased possibility of intracranial hemorrhage and platelet aggregation inhibition as well as an increased risk for clinical hepatitis when the drug is taken in combination with ritonavir [46]. Darunavir and tipranavir are both approved to be used for patients who have not responded to treatment with other ART; when used, these drugs are co-administered with a low dose of ritonavir [47].

Fusion Inhibitors

In 2003, the FDA approved the drug enfuvirtide (Fuzeon), the first new class of anti-HIV drug in seven years. Enfuvirtide, a fusion inhibitor, works by blocking the ability of HIV to infect healthy CD4 cells. When used in combination with other anti-HIV medications, enfuvirtide can reduce the amount of HIV in the blood and increase the number of CD4 cells, slowing the progression of HIV in patients who have developed resistance to currently available medications. Enfuvirtide is administered as a twice-daily subcutaneous injection [48].

CCR5 Antagonists

In August 2007, maraviroc (Selzentry, UK-427) was approved by the FDA for patients with CCR5-tropic HIV-1 infection. Maraviroc is a CCR5 antagonist; it blocks replication of the virus by preventing it from entering noninfected CD4 cells via the predominant route of entry, the CCR5 co-receptor [69]. This medication is intended for use in combination with other antiretroviral agents in treatment-experienced patients with evidence of viral replication and HIV-1 strains resistant to multiple ART [69]. Because both fusion inhibitors and CCR5 antagonists block HIV from entering CD4 cells, they are sometimes grouped together under the category of entry inhibitors.

Integrase Strand Transfer Inhibitors

In 2007, the FDA approved raltegravir, the first agent in a class known as integrase
strand transfer inhibitors, or INSTIs. The FDA approved a second integrase inhibitor,
dolutegravir, in 2013 [27]. These agents
act by preventing the viral DNA from inserting into the host DNA, effectively limiting
infection of additional cells and decreasing viral load [73]. Raltegravir and dolutegravir are approved for use in combination with
other antiretrovirals in treatment-experienced and treatment-naïve patients with evidence
of HIV replication. The integrase inhibitor elvitegravir is only approved to be included
in the combination formulation Stribild; it is not available as a stand-alone
therapy.

INITIATION OF ART

According to the Panel on Antiretroviral Guidelines for Adults and
Adolescents, ART is recommended for all HIV-infected individuals to reduce the risk of
disease progression, with the greatest level of evidence for patients with CD4 counts
<350 cells/mm3.

Strength of Recommendation/Level of Evidence:
AI (Strong recommendation based on one or more randomized trials with clinical
outcomes and/or validated laboratory endpoints)

The decision to initiate ART is one that requires careful discussion with the patient,
usually in consultation with an infectious disease specialist or other physician well-versed
in the use of ART. Physicians and patients alike should be aware of the advantages,
potential toxicities, and complexity of monitoring therapy. At the present time, the most
active triple-drug regimen (for example, two nucleoside analogs and a PI) in a previously
untreated patient can be expected to reduce the viral load below detectable levels, increase
CD4 counts by an average of 100–150/mm3, reduce the risk of
HIV-associated complications, and prolong survival. However, the ability to achieve this
advantage depends on the patient's willingness to accept a complex medical regimen that
requires "many pills," rigorous compliance, frequent follow-up, and moderate risk for drug
toxicity.

One strategy to improve patient compliance has been to combine more than one drug into a
single pill, making it easier for patients to adhere to their medication regimen. Examples
of such drug combinations include Combivir, Epzicom, Trizivir, Truvada, Complera, Atripla,
or Stribild therapy. Trizivir is a fixed-dose combination of Ziagen (abacavir/ABC), Retrovir
(zidovudine/AZT), and Epivir (lamivudine/3TC). Trizivir is not recommended for treatment in
adults or adolescents who weigh less than 40 kilograms because it is a fixed-dose tablet.
Combivir is a combination of zidovudine/AZT and lamivudine/3TC [50,51]. Truvada is a combination of emtricitabine and tenofovir DF, but it is
not recommended for use as part of a triple nucleoside regimen. Truvada has also been
approved for pre-exposure prophylaxis, as will be discussed in detail later in this course.
Epzicom contains both abacavir and lamivudine. Atripla is a combination of one NNRTI and two
NRTIs: efavirenz, tenofovir, and emtricitabine. Complera consists of tenofovir,
emtricitabine, and rilpivirine. Stribild, the first combination containing four drugs,
includes elvitegravir, cobicistat, emtricitabine, and tenofovir.

The approval and availability of the medications listed in this course are subject to change. In addition to those medications that have been FDA-approved for the treatment of HIV, there is a long list of investigational, or "pipeline," drugs being tested in clinical trials. For more information on those agents and the trials, please visit the U.S. Department of Health and Human Services AIDS info website at http://aidsinfo.nih.gov.

Antiretroviral therapy should be initiated for all patients infected with HIV in order
to reduce the risk of disease progression and limit the transmission [42]. The greatest level of evidence for
initiation of therapy is for patients with lower CD4 T-cell counts (<350 cells/mm3), but
there is growing evidence that any untreated HIV infection is associated with development of
non-AIDS-defining diseases [42]. Advances in
the development of antiretroviral medications and combination tablets makes adherence to
therapy more effective, more convenient, and better tolerated than regimens used in the
past. Deferral of therapy may be considered if adherence will be very difficult or
impossible, comorbidities complicate or prohibit antiviral therapy, or a patient is
considered a long-term non-progressor [42].

For treatment-naïve patients, initial recommended therapy generally consists of a regimen
of emtricitabine and tenofovir plus either a PI, an NNRTI, or an INSTI. These regimens
result in maximum reduction of viral load for the longest period of time. When used as
initial therapy, these regimens will achieve the goal of no detectable virus in
approximately 60% to 80% of patients.

The NNRTI-based regimen adds efavirenz, while the INSTI-based therapy includes
dolutegravir or raltegravir. The recommended PI-based regimen consists of tenofovir,
emtricitabine, ritonavir, and either atazanavir or darunavir [42]. Nine additional combinations have been
identified as possible alternative therapies or are recommended for specific patient
populations.

Treatment-experienced patients should be regularly monitored to assess compliance with and effectiveness of the prescribed regimen. For patients who begin to display immunologic failure (inadequate CD4 response despite virologic suppression), switching to a new regimen may be considered [42]. Drug resistance testing should be undertaken to determine if an agent is no longer effective. Untreated coinfections and other medical conditions may contribute to treatment failure.

PREVENTION OF OPPORTUNISTIC INFECTIONS

Depending on the CD4 count and other risk factors, asymptomatic patients may benefit from
treatment to prevent opportunistic infections. In many cases, ART is useful in the
prevention and treatment of these infections. Recommendations for antimicrobial prophylaxis
of opportunistic infections are summarized in Table 3
according to guidelines provided by the CDC, National Institutes of Health, and IDSA [53]. Prophylactic therapy for these conditions
is strongly recommended because these infections are relatively common in HIV patients,
preventive therapy is simple and cost effective, and efficacy has been established in
clinical studies. In addition, all patients should be vaccinated with pneumococcal vaccine.
Hepatitis B vaccination should be considered in patients whose serologic testing indicates
susceptibility.

PROPHYLAXIS TO PREVENT FIRST EPISODE OF OPPORTUNISTIC DISEASE AMONG ADULTS AND
ADOLESCENTS INFECTED WITH HIV

Pathogen

Indication

Preventive Regimen

Preferred*

Alternative

Pneumocystis carinii pneumonia
(PCP)

CD4 count <200 cells/mm3 (AI), or oropharyngeal
candidiasis (AII), or CD4 <14% (BII), or a history of AIDS-defining illness
(BII), or CD4 count >200 but <250 cells/mm3 if
monitoring CD4 cell count every 3 months is not possible (BII)

A positive screening test for LTBI, with no evidence of active TB and no
prior treatment for active TB or LTBI (AI); or close contact with a person with
infectious TB, regardless of screening test results (AII)

Individuals exposed to a sex partner with a diagnosis of primary, secondary,
or early latent syphilis within past 90 days (AII); or individuals exposed to a
sex partner >90 days before syphilis diagnosis in the partner, if serologic
test results are not available immediately and the opportunity for follow-up is
uncertain (AIII)

Patients without chronic HBV or without immunity to HBV (i.e., anti-HBs
<10 IU/mL) (AII); or patients with isolated anti-HBc and negative HBV DNA
(BII). Early vaccination is recommended before CD4 count falls below 350 cells/µL
(AII). However, in patients with low CD4 cell counts, vaccination should not be
deferred until CD4 count reaches >350 cells/mm3,
because some patients with CD4 counts <200 cells/mm3
do respond to vaccination (AII).

PROVIDING CARE FOR THOSE INFECTED

The HIV/AIDS Bureau of the U.S. Department of Health and Human Services has established guidelines for the primary care of patients living with HIV/AIDS. These guidelines stress the importance of establishing mechanisms for coordination and communication to ensure good care for people with HIV/AIDS [58]. A multidisciplinary approach, utilizing the special skills of nurses, pharmacists, nutritionists, social workers, and case managers, is highly desirable to best address patients' needs regarding housing, medical insurance, emotional support, financial benefits, substance abuse counseling, and legal issues.

There are several special issues that often arise in the HIV/AIDS patient population. Because HIV occurs with greater frequency in gay and ethnic minority (particularly black) communities, cultural competency and sensitivity are core elements of care. The guidelines recommend that providers demonstrate respect and provide excellent care to patients with various cultural backgrounds, beliefs, and sexual orientations [58]. Other socioeconomic issues, including poverty, professional and personal stigma, lack of insurance, and illegal immigration status, occur more frequently among these groups and can impact the ability to provide care.

Patient education is a vital aspect of care that begins during the initial evaluation and continues throughout the course of care [58]. Using basic language and verifying patients' understanding of medical terms and concepts can strengthen information provided and ensure that issues are fully addressed. Patient education in the primary care setting should include [58]:

A definition of HIV

Natural history of HIV disease and consequences of immune system destruction

HIV transmission

Interpretation of laboratory results

Indications and goals of treatment, including potential benefits and risks

WOMEN LIVING WITH HIV INFECTION

The route of transmission, clinical manifestations, survival time, and the impact on reproductive health, such as childbearing and gynecologic disease, are all examples of how HIV affects women differently than men. In addition to the clinical manifestations of HIV disease in women, social factors have a significant impact on the health of women with HIV.

The 2014 case definition for HIV infection includes tests and multi-test algorithms that were not available when the AIDS case definition was previously revised. The revised case definition for HIV infection also permits states to report cases to the CDC based on the result of any test licensed for diagnosing HIV infection in the United States [83].

Women make up 24% of those living with HIV in the United
States [28]. The rate of new HIV infections in
women declined 21% between 2008 and 2010, and women accounted for 20% of new cases in 2010.
Women of color have been disproportionately affected by HIV/AIDS. In the United States, the
odds of a woman being diagnosed with HIV in her lifetime are significantly higher for black
women (1 in 32) and Latinas (1 in 106) than for white women (1 in 526) [28]. AIDS is the fourth leading cause of death
among black women 25 to 44 years of age in the United States, but it does not rank among the
top ten leading causes of death among white women in the same age group. Among all women,
those 25 to 34 years of age accounted for the highest number of new infections in 2010 (29%),
followed by women 35 to 44 years of age (25%) and 13 to 24 years of age (22%) [28]. Women are more likely to be infected through
heterosexual intercourse (84% in 2010) than any other type of transmission.

Although AIDS cases have been identified throughout the United States, most are concentrated in large urban areas; for example, approximately two-thirds of cases in Washington are in King County [28,94]. The most rapidly increasing incidence of AIDS is among women who have had heterosexual contact with an HIV-infected man. Cases of woman-to-woman sexual transmission have been reported and are accounted for in the CDC reporting category "other." Other possible modes of transmission that may occur among women include infection through artificial insemination (especially before the availability of HIV testing), sexual abuse or assault, contaminated instruments used for body piercing or tattooing, and healthcare-related occupational exposure. Certain female reproductive tract conditions (e.g., bacterial vaginosis, pelvic inflammatory disease, chlamydia) make HIV more serious.

The risk for acquisition of HIV and the factors that may affect seroconversion in heterosexual women are areas of research. In Europe and the United States, heterosexual monogamous couples with one HIV-infected partner and no other risk factors were followed over time. It was found that female partners of HIV-infected men were 17.5 times more likely to become infected than male partners of infected women. It was also found that the risk for infection increased in couples who did not consistently use latex condoms, were symptomatic, or had low CD4 counts. In other words, women are much more likely to become infected with HIV through heterosexual sex than men, and latex condoms, when used consistently, are an effective means of preventing transmission [55].

TOPICAL MICROBICIDES

Because HIV is spread predominantly through sexual transmission, the development of chemical and physical barriers that can be used intravaginally or intrarectally to inactivate HIV and other STI pathogens is critically important for controlling HIV infection.

Researchers are developing and testing new chemical compounds that women could apply before intercourse to protect themselves against HIV and other sexually transmitted organisms. These include creams or gels, known as topical microbicides, which ideally would be non-irritating and inexpensive. In addition, microbicides should be available in both spermicidal and non-spermicidal formulations so women do not have to put themselves at risk for acquiring HIV and other STIs in order to conceive a child. The research effort for developing topical microbicides includes basic research, preclinical product development, and clinical evaluation.

First-Generation Microbicides

The first microbicides developed to lessen the risk of HIV infection were non-specific entry inhibitors and surfactants [57,62]. These products formed physical barriers in the vagina (surfactants) or changed the vaginal chemistry (pH-modifiers, polyanions), essentially making an environment that is less conducive to the transmission of HIV. First-generation microbicides are gel products that must be applied within a few hours prior to sexual intercourse. Given the complexity of HIV transmission, it is possible that these early microbicides would only be at best 30% to 50% effective [56].

Next-Generation Microbicides

Today, topical microbicide research is focused primarily on new technologies for preventing HIV infection, predominantly the use of antiretroviral agents in the products' formulations. The newer microbicides include NRTIs, NNRTIs, or entry inhibitors to suppress the virus before it begins replication [57,62]. In contrast to the less specific first-generation microbicides, these products are formulated to specifically target HIV.

Because next-generation products may be formulated in sustained-release formulations (e.g., the dapivirine ring), application is not dependent upon planned sexual contact [57]. However, resistance to the antiretroviral agents is a serious concern.

CLINICAL MANIFESTATIONS

Research is being conducted to determine whether the clinical manifestations of HIV, other than those related to the reproductive tract, are different for women than for men. It appears that many symptoms and signs of acute HIV infection and non-specific manifestations, such as fevers, weight loss, and fatigue, are the same. Because past research has either excluded women altogether or included only small cohorts of women, it has been difficult to determine gender differences in the clinical course of HIV disease.

In a large, multicenter cohort study comparing mortality and disease progression between women and men, women were more likely than men to develop bacterial pneumonia, especially if they were injection drug users. In addition, women were more likely to have mycobacterial infections, whereas men had higher rates of oral hairy leukoplakia and Kaposi's sarcoma [55,56].

It is noteworthy that many healthcare providers fail to recognize recurrent vaginal candidiasis as a potential indicator of HIV [56]. This failure to diagnose results in delays in treatment. As many as 60% of HIV-infected women also test positive for some type of human papillomavirus (HPV). HIV infection is a risk factor for higher prevalence of HPV in the cervix and increased likelihood of infection by multiple HPV types. HIV infection is associated with a high rate of cervical cancer and cervical intra-epithelial neoplasia (CIN) or squamous intra-epithelial lesions (SIL). Menstrual irregularities are also frequently reported by women with HIV [56].

PROGNOSIS

Studies have shown that women with AIDS have a poorer prognosis than men, although this is mainly attributed to socioeconomic factors. In a large sample of women and men with HIV, it was found that women had poorer survival rates, although the rates of progression of disease were the same over a 15-month observational period. According to the National Institutes of Health, HIV-positive women whose diagnosis is timely and who receive appropriate treatment have the same survival rate as HIV-infected men [56]. Researchers have speculated that poorer access to or use of healthcare resources (later diagnosis), domestic violence, homelessness, and lack of community support may contribute to the seemingly higher mortality rate for HIV-infected women [56].

ART IN THE HIV-INFECTED PREGNANT WOMAN

The U.S. Preventive Services Task Force recommends that clinicians
screen all pregnant women for HIV, including those who present in labor who are untested
and whose HIV status is unknown.

Strength of Recommendation: A (High
certainty that the net benefit is substantial)

HIV counseling and the offer of HIV testing to pregnant women have been universally recommended in the United States and are now mandatory in some states. Care of the HIV-infected pregnant woman should involve a collaboration between the HIV specialist caring for the woman when she is not pregnant, her obstetrician, and the woman herself. Treatment recommendations for HIV-infected pregnant women are based on the belief that therapies of known benefit to women should not be withheld during pregnancy unless there are known adverse effects on the mother, fetus, or infant that outweigh the potential benefit to the woman [30,31]. Regardless of the stage of pregnancy or childbirth, if a woman is found to be HIV-positive, there are treatment options that should be explored.

Initiation of the following therapy regimens is recommended for pregnant women with HIV in the different stages of pregnancy [31]. Regardless of the stage of pregnancy or childbirth, if a woman is found to be HIV-positive, there are treatment options that should be explored.

Antepartum

The initial assessment of the HIV-positive pregnant woman
should include screening for hepatitis C virus and tuberculosis infection, as well as
history of side effects or toxicities from prior antiretroviral drug regimens [31]. It is recommended that pregnant women
with HIV who have not received prior therapy should begin ART. The decision to continue
therapy for pregnant women who have already been receiving ART should be made
collaboratively. Counseling regarding risks and benefits of ART for the patient and fetus
is recommended, particularly during the first trimester of pregnancy. In general,
continuation of therapy is recommended even if efavirenz is a component of the regimen, as
the adverse effects of the drug are restricted to the first 5 to 6 weeks of pregnancy and
pregnancy is generally not recognized until 4 to 6 weeks post-conception [31]. If therapy is discontinued for the first
trimester, all medications should be discontinued and reintroduced at the same time to
prevent resistance.

As noted, women who are receiving ART who become pregnant should continue their established regimens; replacing potentially teratogenic drugs (i.e., efavirenz, combination stavudine/didanosine) in the first trimester can lead to a loss of viral control and an increased risk of perinatal transmission [31]. Drug-resistance studies should be performed before starting or modifying ARV drug regimens in women whose HIV RNA levels are above the threshold for resistance testing (i.e., >500–1,000 copies/mL). Pregnant patients who have never received ART and with indications for treatment should be started on a regimen as soon as possible after antiretroviral drug resistance testing is completed. If HIV is diagnosed later in pregnancy, ART should be initiated immediately, without waiting for resistance testing results [31]. The recommended ART options are the same as those established for adults with HIV; if possible, zidovudine should be used as part of the initial treatment or another NRTI agent with high placental transfer should be included as a component of the dual-NRTI backbone. Pregnant women with no indications for ART for their own health should also begin treatment as prophylaxis for perinatal transmission, but initiation of therapy may be delayed until after the first trimester [31].

Intrapartum

Several effective administrations are available for women with HIV while in labor. Women who have been receiving ART should continue on the same regimen during the intrapartum period. For HIV-infected women receiving combination antiretroviral regimens who have HIV RNA <400 copies/mL near delivery, zidovudine IV is no longer recommended [31]. Women who have not received ART prior to labor or who have RNA ≥400 copies/mL (or unknown HIV RNA) near delivery should be initiated on a continuous infusion of zidovudine IV during labor, regardless of antepartum regimen or delivery mode. When IV zidovudine is not possible, oral administration should be considered.

Some practitioners also administer a single dose of nevirapine at the onset of labor. Consideration should also be considered for adding lamivudine during labor. One trial showed similar efficacy and safety profiles for these agents, but it is unclear if there is any added benefit of intrapartum administration with either [31].

Postpartum

Infants born to patients who took ART throughout their pregnancies should be administered zidovudine for 6 weeks beginning within 6 to 12 hours of birth. Infants whose mothers had not received ART during pregnancy should be started on zidovudine (4 mg/kg orally, twice daily) for 6 weeks as soon as possible after birth and should be given 3 doses of nevirapine in the first week of life (at birth, 48 hours later, and 96 hours after the second dose) [31]. In addition, these treatment-naïve women should be evaluated for continued ART. In some cases, if antiretroviral medications were administered during labor, zidovudine/lamivudine for 7 days after delivery may be prescribed to mothers to help prevent the development of resistance. Breastfeeding by HIV-infected mothers is not recommended; this includes women on ART [31]. Counseling should be advised for women in the weeks following delivery, as adherence to ART is known to be poor in the postpartum period.

Patients should be registered with the Antiretroviral Pregnancy Registry, which collects observational, nonexperimental data. The registry is sponsored by GlaxoSmithKline, in affiliation with the CDC and Kendle International Inc. Women who have been treated with ART at any time during their pregnancies are eligible for registry enrollment. The telephone number for registration is (800) 258-4263, and the website is http://www.apregistry.com.

INFANTS AND CHILDREN WITH HIV

The initial case reports of pediatric AIDS in infants published in 1983 took much of the world by surprise. Initially, these reports were the subject of much discussion and controversy because many people refused to believe that children could suffer from AIDS. Over the ensuing years, there have been many advances in the recognition, diagnosis, and treatment of pediatric AIDS as well as the unfolding of a pandemic that is a worldwide concern. In the United States, effective screening of blood and improved manufacturing techniques for coagulation factors have eliminated these products as a cause of transmission. In 2010, an estimated 217 children younger than 13 years of age were diagnosed with HIV; 162 (75%) of these children were perinatally infected [59]. Thus, the epidemic in children is closely linked to the epidemic in women [59]. Mother-to-child transmission (MTCT) can occur during pregnancy, labor and delivery, or breastfeeding in both symptomatic and asymptomatic women.

PREVENTION OF PEDIATRIC HIV

The tragedy of MTCT is that women may be unaware of their risk. The CDC has adapted recommendations that advocate universal counseling and testing with informed consent for every pregnant woman regardless of geography, identified risk behavior, or self-identified risk. In 2005, the U.S. Preventative Services Task Force (USPSTF) published guidelines recommending the screening of all pregnant women for HIV. The benefits supporting this statement included a potential for decreased perinatal transmission of HIV resulting from maternal and neonatal ART treatment and the increased opportunity to provide counseling regarding risks associated with breastfeeding and elective cesarean delivery [60].

Many women do not have an identified care provider, lack insurance coverage, seek care only for acute illness, or lack access to ongoing care. Nonetheless, by making counseling and testing a component of routine prenatal care, these recommendations will improve the care given to HIV-infected pregnant women and identify infants at risk for HIV prior to their birth. The American Academy of Pediatrics recommends HIV testing of newborn infants if testing was not offered or accepted by the mother during the prenatal period or if the mother did not receive prenatal care [72]. Testing should be offered confidentially, with counseling and informed consent provided and available healthcare services that are readily accessible.

DIAGNOSIS

The major advances in diagnosis and treatment are profoundly influencing the care of women and children with HIV infection. The documented ability of ZDV to interrupt MTCT has had a tremendous impact on the field of maternal and pediatric HIV. A second major advance is in the diagnosis of HIV infection in infants, which may be completed by 1 month in nonbreastfed infants with the use of virologic assays [84].

In settings throughout the United States, healthcare professionals encounter women and children in their daily practice. Knowledge about and understanding of the nationwide spread of HIV and its implications are crucial. Every pregnant woman must be offered an opportunity to know her HIV status in order to receive the best prenatal care and to assure prompt assessment of her newborn. Although surveys provide a statistical picture, each woman is an individual. HIV testing should always be offered after information and counseling has been provided to the pregnant woman.

More critical than pretest counseling is post-test support. Negative results provide opportunity to reinforce risk. Positive results should always be given in person, never over the phone. If the site is unable to provide continuing services, arrangements must be made for uninterrupted prenatal care that is acceptable to the woman. The diagnosis of HIV is devastating to a pregnant woman, and intense support through an identified friend or family member may be helpful. Depending on the length of gestation, the woman will have many questions regarding the pregnancy as well as her own health.

TREATMENT

The full spectrum of HIV disease in children has become evident as children survive longer. Early in the epidemic, only the most symptomatic and ill children were diagnosed, and so death appeared to occur in infancy and early childhood for most children. It is now recognized that to understand the natural history (disease progression), the progress of infected children must be followed from birth. Several prospective studies in the United States and Europe are following the progress of infants born to HIV-infected women; these cohorts serve as the basis for our description and understanding of the disease in children. Recent reports from these groups show that the median survival for infected children is 8 years, with children with PCP and encephalopathy having the poorest prognosis and the highest mortality in the first year of life. The period from infection to onset of AIDS-defining symptoms is often referred to as the clinical latency period. However, ongoing, complex interaction occurs between the virus and the immune system. The absence of clinical symptoms does not mean that the child is truly "well." Except for age at diagnosis and type of clinical presentation, no demographic or clinical indicators have been related to prognosis. Low CD4 counts for age are the best indicators of immunodeficiency and indicators of the risk of developing opportunistic infections. Early identification of the infected infant, specific prophylactic regimens to prevent infections, and ongoing supportive care are important in improving survival.

Antiretroviral therapy is believed to play a major role in slowing progression of the disease process. Many of the antiretroviral medications approved for use in the treatment of HIV/AIDS are produced in a pediatric formulation [84]. The pharmacologic recommendations for infants and children are based on the same regimens that have been established for adults.

For children younger than 3 years of age, the preferred
NNRTI-based regimen is ritonavir-boosted lopinavir with two NRTIs [84]. The U.S. Department of Health and Human
Services recommends that efavirenz or ritonavir-boosted lopinavir and two NRTIs be used in
the treatment of children 3 to 6 years of age. The preferred PI-based regimen for children
6 years of age or older consists of atazanavir with low-dose ritonavir and two
NRTIs.

Children receiving ART should be monitored for side effects, adherence, efficacy and toxicity. The U.S. Department of Health and Human Services recommends evaluating all pediatric patients within 1 to 2 weeks and again within 1 to 2 months to monitor compliance, side effects, and response to treatment. Subsequently, a visit should be scheduled every 3 to 4 months, and after sustained viral suppression and stable clinical status is established with strict adherence to the regimen, follow-up may be done every 6 to 12 months [84]. Strategies to improve adherence should focus on selecting an appropriate regimen, educating the family/caregiver, and consistent follow-up.

CLINICAL SYMPTOMS IN CHILDREN WITH HIV INFECTION

Children with HIV/AIDS may have more than one infection at the same time or in succession (multiple opportunistic infections). Conditions associated with HIV infection in children are [63,64]:

CLINICAL COURSE

The presence of several HIV-related complications in a child results in physical and psychosocial suffering as well as the need for multiple medications and treatments, including hospitalization. The frequency and intensity of contact with the healthcare providers increase. Physical symptoms include pain (abdominal, headache, extremity, and overall body pain being the most frequently reported), nausea, vomiting, diarrhea, anorexia, loss of function and mobility, weakness, changes in cognition, seizures, shortness of breath and cough, itching, and skin lesions. Psychosocial problems include depression, anger, sorrow, fear, isolation, and ambivalence. Medications and treatments for the disease, although life sustaining, often cause uncomfortable side effects, interfere with quality of life, and produce multiple added stressors for families.

Rapidly progressing disease in the early years of life causes a particular set of complications frequently seen in young children with HIV. These symptoms include failure to thrive with inability to ever achieve appropriate weight and growth, severe progressive encephalopathy with spasticity and developmental delays, severe immune dysfunction, multiple infections, and multi-organ failure. Infants with this group of symptoms often suffer from severe allodynia (painful hypersensitivity to touch), are difficult to console, and frequently cannot be fed by mouth. Such cases pose a significant challenge to caregivers. Pediatric patients with advanced HIV disease frequently have multiple hospitalizations and require treatment with intravenous (IV) medications, either as induction therapy for CMV (retinitis) or as curative therapy for septicemia. Invasive diagnostic studies such as biopsies may be required, or surgical procedures may be needed. Children with advanced HIV disease are most frequently hospitalized for problems such as serious bacterial infections (pneumonia, sepsis, abscesses, sinusitis); new or recurring opportunistic infections (esophagitis, Mycobacterium avium complex, CMV retinitis, herpes); fever and pain of unknown cause; weight loss and nutritional interventions (nasogastric feedings or parenteral nutrition); and hematologic problems such as anemia requiring transfusion, thrombocytopenia requiring infusions of platelets, and intravenous immunoglobulin and neutropenia accompanied by fever.

Critical care is often required when a patient is admitted with a life-threatening illness believed to be treatable. The most common problems requiring critical care are respiratory failure due to PCP or other overwhelming pulmonary infection and septic shock.

OLDER PEOPLE WITH HIV

Approximately 17% of newly diagnosed cases of HIV/AIDS in 2011
occurred in individuals 50 years of age or older, and 39% of all persons living with HIV/AIDS
are 50 years of age or older [15,65]. However, until recently, there had been
little attention given to this group [65].
HIV/AIDS has traditionally been thought to be the disease of the young; therefore, in the
past, prevention and education campaigns had not been targeted toward older adults. However,
evidence points to the increasing number of infected older people and a need for change in
prevention and education campaigns. Some older persons may have less knowledge about HIV and
risk reduction strategies. Due to divorce or being widowed and the availability of medications
to treat erectile dysfunction, increasing numbers of older people are becoming sexually active
with multiple partners [65,66]. For postmenopausal women, contraception is
no longer a concern, and they are less likely to use a condom. Furthermore, vaginal drying and
thinning associated with aging can result in small tears or cuts during sexual activity, which
also raises the risk for infection with HIV/AIDS [67]. Studies indicate that at-risk individuals in this age group are one-sixth
as likely as younger at-risk adults to use condoms during sex [68]. The combination of these factors increases
the risk for unprotected sex with new or multiple partners in this age group, thereby
increasing their risk for AIDS.

This increase must be considered when evaluating older patients. Individuals in this age group are significantly less likely to be tested for HIV [68]. Elderly people presenting with confusion or altered mental status or having severe bouts of pneumonia may first be evaluated for other possibilities before HIV is considered. Many physicians do not suspect HIV in their older patients and miss the opportunity to suggest testing, which can result in delayed diagnosis and treatment.

Early possible signs of immunosuppression that are frequently
overlooked or mistakenly attributed to aging include thrush and skin problems, especially
seborrheic dermatitis, herpes zoster, and recurrent herpes simplex virus type 2 in a person
who does not have a history of it. When HIV is not recognized or treated, the most typical
opportunistic infections are PCP and recurrent bacterial pneumonia, CMV, and Mycobacterium tuberculosis or Mycobacterium
avium complex. PCP can present as bacterial pneumonia, bronchitis, or congestive
heart failure. Early HIV symptoms in the elderly, such as fatigue and weight loss, may appear
to be a normal part of aging, and AIDS-related dementia is often mistaken for Alzheimer's
disease.

AIDS PREVENTION

PRE-EXPOSURE PROPHYLAXIS

In 2012, the FDA approved the first medication for the prevention of sexually transmitted
HIV infection, the combination drug Truvada (emtricitabine/tenofovir DF) [99]. In conjunction with safer sex practices,
Truvada has been found to be partially effective as pre-exposure prophylaxis in high-risk
patients [86]. The Chemoprophylaxis for HIV
Prevention in Men study, also known as iPrEx, studied the effect of once daily Truvada in
2,499 HIV-seronegative men or transgender women who have sex with men compared to placebo
[86]. Researchers found that persons
receiving Truvada experienced a 44% reduction in the incidence of HIV after a median of 1.2
years compared to placebo. Pre-exposure prophylaxis was most effective among participants at
particularly high risk for HIV (i.e., self-reports of unprotected receptive anal
intercourse).

In 2014, the CDC and the U.S. Department of Health and Human Services released clinical
practice guidelines for pre-exposure prophylaxis for the prevention of HIV Infection [44]. This new guideline outlines indications
for prophylaxis as one prevention option for HIV transmission. The most important first step
in determining if an individual is a candidate for pre-exposure prophylaxis is a thorough
history, including sexual and injection drug activities. All candidates will be adults
without an acute or established HIV diagnosis. Pre-exposure prophylaxis is indicated for
high-risk MSM, meaning those who have had any male sex partners in the past 6 months, are
not in a monogamous partnership with a recently tested, HIV-negative man, and have one of
the following [44]:

Anal sex without condoms (receptive or insertive) in the past 6 months

Any STI diagnosed or reported in the past 6 months

An ongoing sexual relationship with an HIV-positive man

Prophylaxis is also recommended for high-risk heterosexual adults who have had sex with an
opposite sex partner(s) in the past 6 months, are not in a monogamous partnership with a
recently tested, HIV-negative partner, and one of the following [44]:

Is a man who has sex with both women and men (behaviorally bisexual)

Infrequently uses condoms during sex with one or more partners of unknown HIV
status who are known to be at substantial risk of HIV infection (IDU or bisexual male
partner)

Is in an ongoing sexual relationship with an HIV-positive partner

IDUs are also considered candidates for pre-exposure prophylaxis if they meet certain
criteria. The guideline states that persons who have injected drugs not prescribed by a
clinician in past 6 months may be candidates for prophylaxis if they also are positive for
one of the following factors [44]:

Any sharing of injection or drug preparation equipment in the past 6 months

Been in a methadone, buprenorphine, or buprenorphine/naloxone treatment program in
the past 6 months

Only fixed-dose combination tenofovir and emtricitabine (Truvada) taken daily is approved
for pre-exposure prophylaxis, and it is considered the recommended first-line option [44,99]. However, because tenofovir alone has been proven effective in trials
with IDU and heterosexually active men and women, it is the alternative option for these
populations [44]. No other antiretroviral
regimens should be used for pre-exposure prophylaxis.

All patients prescribed Truvada for pre-exposure prophylaxis must have a negative HIV
test prior to initiating treatment and every 3 months thereafter. In addition, patients
should be advised regarding possible side effects and the continued necessity for safe sex
practices. Eligible patients should also be screened for hepatitis B and have a confirmed
creatinine clearance of 60 mL per minute or greater [44].

AIDS VACCINE

Achieving an end to the AIDS epidemic will require the development of an effective vaccine. Both preventive and therapeutic vaccines are being studied for use in the fight against HIV. Preventive vaccines are developed to protect individuals from contracting HIV, while the goal of therapeutic vaccines is to boost immune response to and better control existing HIV infection [71]. Of course, the ultimate goal in vaccine research is a vaccine that will prevent infection; however, despite several trials, no vaccine effective in preventing HIV has been discovered.

There are three types of preventive vaccines being studied for the prevention of HIV: subunit vaccines, recombinant vector vaccines, and DNA vaccines [70]. Subunit vaccines, also known as component or protein vaccines, contain only genetically engineered parts of HIV rather than the whole virus. Theoretically, these parts, or subunits, may induce an anti-HIV immune response, but the effectiveness of preventing future infection is unknown.

DNA vaccines contain a portion of a virus's genetic material. The partial HIV DNA is injected into the body, where existing cells produce HIV proteins. As a result, the body produces an immune response against HIV.

Finally, recombinant vector vaccines utilize as attenuated non-HIV virus, or vector, to carry a portion of HIV's genetic material into the recipient's body. As with the DNA vaccines, the HIV genes create proteins, which in turn stimulate an immune response. Because most HIV recombinant vector vaccines deliver several HIV genes, they may create a stronger immune response. Canarypox virus, cowpox virus, Venezuelan equine encephalitis, and adenovirus-5 are all being studied as possible vectors for future HIV vaccines [70].

The possibility of combining two or more types of vaccines in a booster system to strengthen immune response is being studied. This prime-boost vaccination strategy may stimulate different parts of the immune system and enhance the effectiveness of the vaccines [70].

It is important to note that none of these vaccines contains the viral material necessary to develop HIV infection. Those vaccines that contain genetic material from the virus do not carry the full virus or the complete set of genes necessary for infection [70].

The International AIDS Vaccine Initiative (IAVI) is working to speed the development and distribution of preventive AIDS vaccines, focusing on four areas: mobilizing support through advocacy and education; accelerating scientific progress; encouraging industrial participation in AIDS vaccine development; and assuring global access.

EDUCATION AND INTERVENTION TO PREVENT HIV/AIDS INFECTION

Many adolescents engage in behaviors that put them at risk for HIV infection. According to the CDC, nearly 50% of high school students have engaged in intercourse [91]. Approximately 40% of sexually active high school students had not used a condom at last sexual intercourse; 2.3% had ever injected an illegal drug [91]. The CDC asserts that renewed educational efforts that reach all students before risk behaviors are initiated and that seek to delay the onset of sexual activity, increase condom use among students who are sexually active, and decrease injection drug use are warranted [91]. Education and interventions are considered vital to the reduction of high-risk behaviors in this population.

Although more than 90% of adolescents report having received education on HIV prevention in school, the content of these discussions may not provide adequate information on the subject. Furthermore, the American Academy of Pediatrics determined that school-based education and intervention programs do not provide the necessary opportunities for confidential discussions or targeted counseling [93]. Healthcare professionals have a unique opportunity to intervene in this population to provide accurate and complete information on HIV transmission and risk reduction.

The CDC HIV/AIDS Prevention Research Synthesis Project collects and analyzes systematic reviews and identifies evidence-based interventions that have been proven effective in eliminating or reducing sex- or drug-related risk behaviors, reducing the rate of new HIV/STD infections, or increasing HIV-protective behaviors [92]. As of 2014, 82 best-evidence interventions had been identified, many of which target specific populations. Intervention packages and more information on these interventions are available at http://www.cdc.gov/hiv/dhap/prb/prs.

HIV/AIDS REPORTING

The state of Washington has specific laws and statutes governing HIV testing, including sections devoted to informed reporting, consent, and confidentiality. According to the Washington Administrative Code, healthcare professionals must report diagnoses of HIV and/or AIDS local health departments within 3 business days [95]. According to the Washington Department of Health, laboratories are required to report each test result (except in King County or when another local health department is designated by the Department of Health), including [96]:

For each result, the lab must provide the test result, date of collection, requesting health care provider, and patient information including name, sex, date of birth, address, and telephone number. As of July 1, 2011, healthcare providers requesting a laboratory test for HIV/AIDS are required to provide the following information [95]:

Patient name

Patient address including zip code

Patient date of birth

Patient sex

Name of the principal healthcare provider

Telephone number of the principal healthcare provider

Type of test requested

Type of specimen

Date of ordering specimen collection

Many HIV and AIDS case reports are initiated from a laboratory result. However, when testing takes place outside of Washington, it is the healthcare provider's responsibility to ensure that the diagnosis is reported to the public health office. According to Washington Administrative Code, in these cases healthcare providers can meet this requirement by arranging for the referral laboratory to notify either the local health department, the department, or both; or forwarding the notification of the test result from the referral laboratory to the local health department, the department, or both [95].

WASHINGTON STATUTES

Knowledge of statutes related to HIV/AIDS testing, reporting, and counseling may be useful
in ensuring that public health is served and patients' rights are protected. To view the
Washington Administrative Code Chapters 246-100 and 246-101 pertaining to communicable and
notifiable diseases, please visit the Washington Legislature's website at http://apps.leg.wa.gov/wac/default.aspx?cite=246.

CONCLUSION

Although prevention and new medical interventions may reduce the pace of the epidemic, HIV
will be a significant disease for many years both in the United States and the world.
Education provides the opportunity to ensure that healthcare professionals have the
information necessary to provide the best possible care for persons with HIV. Healthcare
administrators have the responsibility to recognize the special stresses, and the generic
ones, associated with caring for HIV patients and to address those with meaningful changes in
case load and staff support. Those who specialize in HIV care must identify ways to renew
themselves through education, individual support, staff support, and variation of workload so
that they can continue to contribute their valuable expertise to patients with HIV. With no
easy cure in sight, healthcare professionals have the opportunity to work with patients to
help them achieve and maintain their optimal level of health throughout the continuum of HIV
disease.

19. Centers for Disease Control and Prevention. Press Release: National HIV Prevention Conference Echoes Themes of HHS New HIV Prevention Initiative. Available at http://www.cdc.gov/media/pressrel/r030728.htm. Last accessed March 11, 2014.

31. Perinatal HIV Guidelines Working Group. Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Washington, DC: National Institutes of Health; 2012. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf. Last accessed March 14, 2014.

44. Centers for Disease Control and Prevention. Preexposure Prophylaxis for the
Prevention of HIV Infection in the United States, 2014: A Clinical Practice Guideline.
Available at http://www.cdc.gov/hiv/pdf/prepguidelines2014.pdf. Last accessed November 12,
2014.

53. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the Prevention and Treatment of Opportunistic Infections in
HIV-Infected Adults and Adolescents: Recommendations from the Centers for Disease Control
and Prevention, the National Institutes of Health, and the HIV Medicine Association of the
Infectious Diseases Society of America. Atlanta, GA: Centers for Disease
Control and Prevention; 2013. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Last accessed
November 12, 2014.

54. Agency for Health Care Policy and Research. Many People with AIDS Change Their Minds About End-of-Life Care as the Disease Progresses. 1999. Available at http://archive.ahrq.gov/research/apr99/ra11.htm. Last accessed March 17, 2014.

84. Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Rockville, MD: Department of Health and Human Services; 2014.

93. American Academy of Pediatrics Committee on Psychosocial Aspects of Child and Family Health and Committee on Adolescence. Sexuality education for children and adolescents. Pediatrics. 2001;108(2):498-502.

94. HIV/AIDS Epidemiology Unit, Public Health-Seattle and King County and the Infectious Disease and Reproductive Health Assessment Unit, Washington State Department of Health. HIV/AIDS Epidemiology Report, First Half 2013: Volume 82. Olympia, WA: Washington State Department of Health; 2013.

Evidence-Based Practice Recommendations Citations

1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Bethesda, MD: U.S. Department of Health and Human Services; 2013. Summary retrieved from National Guideline Clearinghouse at http://www.guideline.gov/content.aspx?id=43783. Last accessed March 24, 2014.

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